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Basso, Valentina (2018) Regulation of ER-Mitochondria tethering in an in vivo animal model of Parkinson's disease. [Ph.D. thesis]

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Abstract (english)

Mitochondria form a tubular, reticulated network which shape is controlled by opposing fusion and fission events (Bereiter-Hahn and Voth, 1994). The mitofusins 1 and 2 (Mfn1 and Mfn2) are conserved, dynamin-like GTPases embedded in the outer mitochondrial membrane (OMM) that mediate mitochondrial fusion in coordination with OPA1 (Rojo et al., 2002; Santel and Fuller, 2001; Wong et al., 2000). Mitochondrial shaping proteins have pleiotropic functions. In particular, while Mfn1 seems primarily involved in organellar docking and fusion, Mfn2 is enriched at contact sites between ER and mitochondria where it is implicated in the formation of molecular linkers that are capable of organelles tethering (Chen et al., 2012; de Brito and Scorrano, 2008). Recent works attributed to these points of close contact between the OMM and the nearby ER, called MAMs (mitochondria-associated ER-membranes) or MERCs (mitochondria-ER contacts), an important role in the propagation of cellular signals, including those that control lipid metabolism, calcium (Ca2+) homeostasis and cell death (Rowland et al., 2012; Rizzuto et al., 1998; Vance, 1990). Indeed, aberrations in ER-mitochondria juxtaposition have been described in cellular models of different neurodegenerative diseases, including Alzheimer's, Huntington's and Parkinson's disease (Krols et al., 2016; Calì et al., 2013; Ottolini et al., 2013; Area-Gomez et al., 2012; Calì et al., 2012; Panov et al., 2002). Although the exact cause for neuronal loss is not clear
Parkin, an E3-ubiquitin ligase mutated in familiar Parkinson's Disease (PD) is selectively recruited to dysfunctional mitochondria and promotes their elimination via autophagy, a process known as mitophagy (Narendra et al., 2008). PINK1, a protein kinase, also a PD related gene, is required for Parkin recruitment and stress induced mitophagy (Ziviani et al., 2010). In several model systems, Parkin selectively ubiquitinates the mitochondrial outer membrane profusion protein Mfn1 and Mfn2 and fly homologue Marf (Tanaka et al., 2010; Ziviani et al., 2010; Gegg et al., 2010). Accordingly, lack of Parkin or PINK1, which operates upstream Parkin in the same pathway, results in impaired ubiquitination of Mfn and increased levels of Mfn (Ziviani et al., 2010).
Given that Parkin affects Mfn steady state and ubiquitination levels, we propose to (i) address the ubiquitination levels of Mfn2 and whether Parkin downregulation affects it; (ii) investigate whether Parkin regulates ER-mitochondria tethering by impinging on Mfn2 steady state and ubiquitination levels; (iii) evaluate the physiological significance of ER-mitochondria interaction in an in vivo animal model of Parkinson's disease.
Our hypothesis is that Parkin dependent Mfn ubiquitinatination controls ER-mitochondria tethering, thus impinging on Ca2+ transfer and Ca2+ homeostasis, which dysregulation has been described in a number of molecular pathways leading to PINK1 and Parkin loss of function dependent neurodegeneration (Calì et al., 2013; Ottolini et al., 2013; Calì et al., 2012).
In order to address the previously listed hypothesis we analysed the pattern of ubiquitination of Mfn2 in mouse embryonic fibroblasts (MEFs) upon downregulation of Parkin. To this aim, we (i) immunoprecipitated Mfn2 with specific anti Mfn2 antibody and performed western blotting analysis with specific anti HA antibody in cells overexpressing HA tagged Ubiquitin; (ii) measured the degree of tethering between ER and mitochondria in control and Parkin downregulating cells. We used two independent approaches to measure ER-mitochondria tethering: we first measured the percentage of ER co-localizing with mitochondria by using Mander's coefficient of co-localization upon volume-rendered 3D reconstruction of z-axis stacks of confocal images of cells expressing organelles targeted fluorescence probes (mito-RFP and ER-YFP, respectively) (Rizzuto et al., 1998). Secondly, we took advantage of a FRET based probe (Naon et al., 2016) to measure ER-mitochondria proximity. In this sensor, called FEMP, FRET intensity is inversely proportional to the distance between the two fluorophores (mito-YFP and ER-CFP) that are appropriately targeted to the two compartments. (iii) We investigated the physiological significance of ER-mitochondria tether in an in vivo animal model of PD that lacks PINK1 expression. To this aim we used the fruitfly Drosophila melanogaster, which has many advantages. First, fly mutants deriving from loss of function mutations of PINK1 have been extensively characterized and cause a robust phenotype represented by age-related degeneration of DA neuron loss and locomotor deficits (Poole et al., 2008; Clark et al., 2006; Park et al., 2006; Yang et al., 2006; Wang et al., 2006). Secondly, a variety of genetic modifications and epistasis experiments can be easily performed in vivo to dissect molecular pathways.
Our results showed that Parkin downregulation reduced Mfn ubiquitination and ER-mitochondria tethering in MEFs. Interestingly, we found that the pattern of Mfn2 ubiquitination and ER-mitochondria tethering is also impaired in CMT type 2A disease-associated Mfn2 mutations (Mfn2R94Q, Mfn2P251A and Mfn2R280H respectively). Although indirectly, these findings strongly suggested that ubiquitination of Mfn2, rather than its steady state levels, is important in the regulation of ER-mitochondria tethering.
To identify the precise site of Mfn2 ubiquitination and directly link lack of ubiquitination with impaired ER-mitochondria tether, we took advantage of a bioinformatics approach to identify among species-highly conserved lysine (K) residues. We identified twenty Lysine residues that were conserved between human, mouse and fly. We compared these residues with those identified by a mass spectrometry-based study published in 2014 (Bingol et al., 2014) that identified Parkin-dependent ubiquitination sites. We identified six Lysine residues that were likely to represent good candidates for Parkin-dependent ubiquitination of Mfn2. We generated non-ubiquitinatable mutants for those sites by substituting Lysine (K) with Arginine (R), a common procedure to impair ubiquitination and investigated the pattern of ubiquitination of the non-ubiquitinatable Mfn2 mutants by western blotting. Expression of non-ubiquitinable mutant K416R resulted in impaired Mfn2 ubiquitination. Of note this mutant was also unable to correct ER-mitochondrial contacts when expressed in Mfn2 KO MEFs and only partial restored ER-mitochondrial Ca2+ transfer.
In summary, our results provided strong evidences that Mfn2 ubiquitination is a prerequisite for ER-mitochondria physical and functional interaction and that K416 in the HR1 domain of Mfn2 is a genuine site for Parkin dependent ubiquitination.
A number of studies have shown impaired Ca2+ homeostasis in cellular models lacking PINK1 or Parkin (Heeman et al., 2011; Sandebring et al., 2009). Although it is not clear why dopaminergic neurons specifically degenerate in PD, it is tempting to hypothesis that impaired Ca2+ homeostasis resulting from impaired Ca2+ cross talk at ER-mitochondria interface could lead or contribute to degeneration. Elegant studies have shown that artificial tether between ER and mitochondria can be used to modulate Ca2+ transfer (Csordas et al., 2010; Csordas et al., 2006). With that in mind, we addressed whether expressing an ER-mitochondria synthetic linker in a well-established in vivo Drosophila model of PINK1 loss of function could ameliorate PINK1 KO phenotypes by impinging on ER-mitochondria cross talk. We therefore generated a number of fly lines expressing the synthetic linker driven by a neuron-specific driver in the fly wing neurons. This linker was generated by Csordas et al. (Csordas et al., 2006) and consists of a monomeric fluorescent protein (RFP) fused to the outer mitochondrial membrane targeting sequence at the N terminus and fused to the ER targeting sequence at the C terminus. We could observe a well-defined and easily quantifiable RFP-fluorescence spots throughout the L1 vein of the fly wing that perfectly matched the morphology seen when expressing mito-GFP or ER-GFP alone in the wing neurons (Vagnoni and Bullock, 2016), which indicated that the synthetic linker was appropriately expressed.
Interestingly, we found an amelioration of PINK1 KO climbing ability upon expression of the artificial synthetic linker. This result strong indicates that restoration of proper ER-mitochondrial communication in PINK1 KO background can be beneficial in ameliorating the phenotype associated to an in vivo animal model of PD, paving the way for novel approaches for medical intervention.

Abstract (italian)

I mitocondri formano un network reticolare e tubulare la cui forma è controllata da eventi opposti di fusione e fissione (Bereiter-Hahn and Voth, 1994). Le mitofusine 1 e 2 (Mfn1 e Mfn2), sono delle GTPasi dynamin-like incorporate nella membrana mitocondriale esterna (OMM, outer mitochondrial membrane) e mediano la fusione mitocondriale in cooperazione con OPA1 (Rojo et al., 2002; Santel and Fuller, 2001; Wong et al., 2000). Le shaping protein mitocondriali hanno una funzione pleiotropica. In particolare, mentre la Mfn1 sembra principalmente coinvolta nel docking e nella fusione di organelli, la Mfn2 è arricchita nei punti di contatto tra ER e mitocondri dove è implicata nella formazione di collegamenti molecolari che sono capaci di produrre un'interazione tra gli organelli (Chen et al., 2012; de Brito and Scorrano, 2008). Lavori recenti attribuiscono a questi punti di stretto contatto tra l'OMM e il vicino ER, chiamati MAMs (mitochondria-associated ER-membranes) o MERCS (mitochondria-ER contacts), un importante ruolo nella propagazione del segnale cellulare, incluso quello che controlla il metabolismo lipidico, l'omeostasi del calcio (Ca2+) e la morte cellulare (Rowland et al., 2012; Rizzuto et al., 1998; Vance, 1990). Un'anomalia nella comunicazione tra ER e mitocondri è stata descritta in vari modelli cellulari di differenti malattie neurodegenerative, che includono la malattia di Alzheimer, Huntington e Parkinson (Krols et al., 2016; Calì et al., 2013; Ottolini et al., 2013; Area-Gomez et al., 2012; Calì et al., 2012; Panov et al., 2002). Tuttavia la causa esatta che induce la perdita neuronale non è ancora conosciuta.
Parkin, una E3-ubiquitina ligasi mutata nelle forme familiari di malattia di Parkinson (PD, Parkinson's disease) è selettivamente reclutata sui mitocondri disfunzionali e promuove la loro eliminazione tramite autofagia, un processo conosciuto come mitofagia (Narendra et al., 2008). PINK1, una proteina chinasica e gene associata alla PD, è richiesto per il reclutamento di Parkin e per la mitofagia indotta da stress (Ziviani et al., 2010). Nei diversi sistemi modello, Parkin ubiquitina selettivamente le proteine ancorate sulla membrana mitocondriale esterna che promuovono la fusione (Mfn1 e Mfn2) e il loro omologo in Drosophila (Marf) (Tanaka et al., 2010; Ziviani et al., 2010; Gegg et al., 2010). Di conseguenza, l'assenza di Parkin o PINK1, il quale opera a monte di Parkin nella stessa pathway, causa un'alterazione nell'ubiquitinazione della Mfn e un aumento dei livelli di Mfn (Ziviani et al., 2010).
Dato che Parkin altera i livelli basali e di ubiquitinazione della Mfn, noi abbiamo proposto di (i) valutare i livelli di ubiquitinazione della mitofusina ed analizzare se la downregolazione di Parkin ha effetti su questi livelli; (ii) investigare se Parkin regola il legame tra ER e mitocondri andando ad agire sui livelli stazionari o di ubiquitinazione della Mfn2; (iii) valutare il significato fisiologico dell'interazione ER-mitocondri in un modello animale in vivo di malattia di Parkinson.
La nostra ipotesi è che l'ubiquitinazione della Mfn Parkin-dipendente controlli il legame ER-mitocondri, interferendo così con il trasferimento e l'omeostasi di Ca2+, la cui alterazione è stata descritta in numerose pathway molecolari che causano neurodegenerazione associata alla perdita di funzionalità  di PINK1 e Parkin (Calì et al., 2013; Ottolini et al., 2013; Calì et al., 2012).
Al fine di affrontare la precedente lista di ipotesi abbiamo analizzato i livelli di ubiquitinazione della Mfn2 in fibroblasti embrionali di topo (MEFs: mouse embryonic fibroblasts) in seguito alla downregolazione di Parkin. A questo scopo, abbiamo (i) immunoprecipitato la Mfn2 con lo specifico anticorpo anti Mfn2 ed eseguito il western blotting con lo specifico anticorpo anti HA in cellule overesprimenti l'ubiquitina taggata HA; (ii) misurato i livelli di connessione tra ER e mitocondri nelle cellule di controllo e in cellule con Parkin downregolato. Abbiamo utilizzato due approcci indipendenti per misurare questa connessione: per prima cosa abbiamo misurato la percentuale di co-localizzazione dell'ER con i mitocondri usando il coefficiente di co-localizzazione di Mander in seguito alla ricostruzione volumetrica 3D delle immagini confocali lungo l'asse z di cellule esprimenti le sonde fluorescenti bersaglio degli organelli (rispettivamente, mito-RFP and ER-YFP) (Rizzuto et al., 1998). In secondo luogo, abbiamo sfruttato una sonda basata su FRET (Naon et al., 2016) per misurare la vicinanza dell'ER con i mitocondri. In questo sensore, chiamato FEMP, l'intensità  di FRET è inversamente proporzionale alla distanza tra i due fluorofori (mito-YFP e ER-CFP) che sono opportunamente indirizzati ai due compartimenti. (iii) Abbiamo studiato il significato fisiologico dell'interazione ER-mitocondrio in un modello animale in vivo di PD privo dell'espressione di PINK1. A questo scopo abbiamo usato la Drosophila melanogaster, che ha molti vantaggi. Innanzitutto i mutanti di Drosophila, derivati da mutazioni che causano la perdita di funzionalità  di PINK1, sono stati ampiamente caratterizzati ed inducono un fenotipo robusto rappresentato dalla perdita dei neuroni DA e deficit locomotori correlati all'età  (Poole et al., 2008; Clark et al., 2006; Park et al., 2006; Yang et al., 2006; Wang et al., 2006). In secondo luogo, in vivo possono essere facilmente eseguiti un'ampia varietà  di modifiche genetiche ed esperimenti di epistasi per comprendere più approfonditamente le pathway molecolari.
I nostri risultati mostrano che in MEFs la downregolarione di Parkin riduce l'ubiquitinazione della Mfn e l'interazione tra ER e mitocondri. Abbiamo osservato inoltre che le mutazioni della Mfn2 associate a CMT di tipo 2A (rispettivamente Mfn2R94Q, Mfn2P251A e Mfn2R280H) causano l'alterazione dei livelli di ubiquitinazione della Mfn2 ed una diminuzione nell'interazione tra ER e mitocondri. Sebbene indirettamente, questi risultati suggeriscono fortemente che l'ubiquitinazione della Mfn2, piuttosto che i livelli stazionari, è importante nella regolazione dell'interazione tra ER e mitocondri.
Per identificare il sito preciso di ubiquitinazione della Mfn2 e correlare direttamente la mancanza dell'ubiquitinazione con la riduzione dell'interazione ER-mitocondri, abbiamo sfruttato un approccio bioinformatico che ci ha permesso di individuare i residui di lisina (K) altamente conservate nelle varie specie. Abbiamo identificato venti residui di lisina che sono conservati tra uomo, topo e Drosophila. Abbiamo confrontato questi residui con quelli descritti in uno studio basato sull'utilizzo della spettrometria di massa per identificare i siti di ubiquitinazione dipendenti da Parkin pubblicato nel 2014 (Bingol et al., 2014). Abbiamo identificato sei residui di lisina che potrebbero rappresentare dei buoni candidati per l'ubiquitinazione Parkin-dipendente della Mfn2. Abbiamo generato i mutanti non ubiquitabili per questi siti sostituendo la lisina (K) con l'arginina (R), una procedura comune per bloccare l'ubiquitinazione e studiato il pattern di ubiquitinazione dei mutanti Mfn2 non ubiquitinabili mediante western blotting.
L'espressione del mutante non ubiquitinabile K416R ha provocato un'alterazione dell'ubiquitinazione della Mfn2. Da notare che questo mutante non è stato in grado di ripristinare i contatti ER-mitocondri quando reintrodotto in MEF Mfn2 KO ed ha restaurato solo parzialmente il trasferimento di Ca2+ ER-mitocondriale. In breve, i nostri risultati hanno fornito prove evidenti che l'ubiquitinazione di Mfn2 è un prerequisito per l'interazione fisica e funzionale dei mitocondri con l'ER e che la K416 nel dominio HR1 della Mfn2 è un vero e proprio sito per l'ubiquitinazione Parkin-dipendente.
Vari studi hanno osservato in diversi modelli cellulari privi di PINK1 o Parkin un'alterata omeostasi del Ca2+ (Heeman et al., 2011; Sandebring et al., 2009). Sebbene non sia chiaro il motivo per il quale nel PD degenerino specificatamente i neuroni dopaminergici è allettante ipotizzare che un deficit nell'omeostasi del Ca2+, risultante da un alterato scambio di Ca2+ nell'interfaccia ER-mitocondrio, possa portare o contribuire alla degenerazione. Eleganti studi hanno dimostrato che un legame artificiale tra ER e mitocondri può essere usato per modulare il trasferimento di Ca2+ (Csordas et al., 2010; Csordas et al., 2006). Tenendo questo a mente, ci siamo occupati del fatto che l'espressione di un legante sintetico tra ER e mitocondri in un modello in vivo di Drosophila PINK1 loss of function potesse migliorare il fenotipo dei PINK1 KO incidendo sulla comunicazione ER-mitocondriale. Per questo motivo abbiamo generato un certo numero di linee di Drosophila esprimenti il linker sintetico guidato da uno specifico driver neuronale nei neuroni delle ali. Questo linker è stato generato da Csordas et al. (Csordas et al., 2006) e consiste in una proteina monomerica fluorescente (RFP) fusa all'N terminale con la sequenza bersaglio della membrana mitocondriale esterna e fusa al C-terminale con la sequenza bersaglio dell'ER. Abbiamo potuto visualizzare e quantificare i punti di fluorescenza RFP lungo la vena L1 nell'ala della Drosophila dimostrando una corrispondenza con la morfologia osservata a seguito dell'espressione di mito-GFP o ER-GFP sui neuroni dell'ala (Vagnoni e Bullock, 2016), indice del fatto che l'espressione del linker sintetico era appropriata.
E' interessante notare che abbiamo osservato un miglioramento dell'abilità  di arrampicata della Drosophila PINK1 KO in seguito all'espressione del linker sintetico artificiale. Questo risultato indica che il ripristino della corretta comunicazione tra ER e mitocondri nel background PINK1 KO può essere utile per migliorare il fenotipo associato ad un modello animale in vivo di PD, aprendo la strada a nuovi approcci per l'intervento medico.

EPrint type:Ph.D. thesis
Tutor:Ziviani, Elena
Ph.D. course:Ciclo 30 > Corsi 30 > BIOSCIENZE
Data di deposito della tesi:15 January 2018
Anno di Pubblicazione:15 January 2018
Key Words:Mitochondria, Parkinson's disease, ER-mitochondria tethering, Mitofusin, Parkin, PINK1, ubiquitination, ER-mitochondria synthetic tether, Drosophila model of PD.
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/10 Biochimica
Area 05 - Scienze biologiche > BIO/11 Biologia molecolare
Struttura di riferimento:Dipartimenti > Dipartimento di Biologia
Codice ID:10786
Depositato il:08 Nov 2018 11:08
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I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

Abou-Sleiman PM, Muqit MM, Wood NW. Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat Rev Neurosci 2006; 7(3):207-19. Cerca con Google

Adams MD, Sekelsky JJ. From sequence to phenotype: reverse genetics in Drosophila melanogaster. Nat Rev Genet 2002; 3(3):189-98. Cerca con Google

Ahn BH, Rhim H, Kim SY, Sung YM, Lee MY, Choi JY, Wolozin B, Chang JS, Lee YH, Kwon TK, Chung KC, Yoon SH, Hahn SJ, Kim MS, Jo YH, Min DS. alpha-Synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells. J Biol Chem 2002; 277(14):12334-42. Cerca con Google

Akundi RS, Huang Z, Eason J, Pandya JD, Zhi L, Cass WA, Sullivan PG, Bueler H. Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice. PLoS One 2011; 6(1):e16038. Cerca con Google

Anton F, Dittmar G, Langer T, Escobar-Henriques M. Two deubiquitylases act on mitofusin and regulate mitochondrial fusion along independent pathways. Mol Cell 2013; 49(3):487-98. Cerca con Google

Area-Gomez E, Del Carmen Lara Castillo M, Tambini MD, Guardia-Laguarta C, de Groof AJ, Madra M, Ikenouchi J, Umeda M, Bird TD, Sturley SL, Schon EA. Upregulated function of mitochondria-associated ER membranes in Alzheimer disease. EMBO J 2012; 31(21):4106-23. Cerca con Google

Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, Koteliansky V, Mootha VK. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 2011; 476(7360):341-5. Cerca con Google

Beal MF. Mitochondria, oxidative damage, and inflammation in Parkinson's disease. Ann N Y Acad Sci 2003; 991:120-31. Cerca con Google

Beilina A, Van Der Brug M, Ahmad R, Kesavapany S, Miller DW, Petsko GA, Cookson MR. Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability. Proc Natl Acad Sci U S A 2005; 102(16):5703-8. Cerca con Google

Bereiter-Hahn J, Voth M. Dynamics of mitochondria in living cells: shape changes, dislocations, fusion, and fission of mitochondria. Microsc Res Tech 1994; 27(3):198-219. Cerca con Google

Berry C, La Vecchia C, Nicotera P. Paraquat and parkinson's disease. Cell Death Differ 2010; 17(7):1115-25. Cerca con Google

Bertoncini CW, Fernandez CO, Griesinger C, Jovin TM, Zweckstetter M. Familial mutants of a-synuclein with increased neurotoxicity have a destabilized conformation. J Biol Chem 2005; 280(35):30649-52. Cerca con Google

Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 2000; 3(12):1301-6. Cerca con Google

Bezard E, Imbert C, Deloire X, Bioulac B, Gross CE. A chronic MPTP model reproducing the slow evolution of Parkinson's disease: evolution of motor symptoms in the monkey. Brain Res 1997; 766(1-2):107-12. Cerca con Google

Bezard E, Przedborski S. A tale on animal models of Parkinson's Disease. Mov Disord 2011; 26(6):993-1002. Cerca con Google

Bingol B, Tea JS, Phu L, Reichelt M, Bakalarski CE, Song Q, Foreman O, Kirkpatrick DS, Sheng M. The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature 2014; 510(7505):370-5. Cerca con Google

Bjorklund A, Dunnett SB. Dopamine neuron systems in the brain: an update. Trends Neurosci 2007; 30(5):194-202. Cerca con Google

Blandini F, Armentero MT, Martignoni E. The 6-hydroxydopamine model: news from the past. Parkinsonism and Related Disorders 2008; 14(2):S124-S129. Cerca con Google

Bleazard W, McCaffery JM, King EJ, Bale S, Mozdy A, Tieu Q, Nunnari J, Shaw JM. The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nat Cell Biol 1999; 1(5):298-304. Cerca con Google

Blesa J and Przedborski S. Parkinson's disease: animal models and dopaminergic cell vulnerability. Front Neuroanat 2014; 8: 155. Cerca con Google

Blum D, Torch S, Lambeng N, Nissou M, Benabid AL, Sadoul R, Verna JM. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: Contribution to the apoptotic theory in Parkinson's disease. Prog Neurobiol 2001; 65(2):135-72. Cerca con Google

Boehning D, Patterson RL, Sedaghat L, Glebova NO, Kurosaki T, Snyder SH. Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis. Nat Cell Biol 2003; 5(12):1051-61. Cerca con Google

Bogaerts V, Theuns J, van Broeckhoven C. Genetic findings in Parkinson's disease and translation into treatment: a leading role for mitochondria? Genes Brain Behav 2008; 7(2):129-51. Cerca con Google

Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res 2004; 318(1):121-34. Cerca con Google

Brand AH, Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 1993; 118(2):401-15. Cerca con Google

Brooks AI, Chadwick CA, Gelbard HA, Cory-Slechta DA, Federoff HJ. Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res 1999; 823(1-2):1-10. Cerca con Google

Calì T, Ottolini D, Negro A, Brini M. Alpha-synuclein controls mitochondrial calcium homeostasis by enhancing endoplasmic reticulum-mitochondria interactions. J Biol Chem 2012; 287(22):17914-29. Cerca con Google

Calì T, Ottolini D, Negro A, Brini M. Enhanced parkin levels favor ER-mitochondria crosstalk and guarantee Ca(2+) transfer to sustain cell bioenergetics. Biochim Biophys Acta 2013; 1832(4):495-508. Cerca con Google

Calì T, Ottolini D, Negro A, Brini M. Alpha-Synuclein controls mitochondrial calcium homeostasis by enhancing endoplasmic reticulum-mitochondria interactions. J Biol Chem 2012; 287(22):17914-29. Cerca con Google

Cannon JR, Tapias V, Na HM, Honick AS, Drolet RE, Greenamyre JT. A highly reproducible rotenone model of Parkinson's disease. Neurobiol Dis 2009; 34(2):279-90. Cerca con Google

Castello PR, Drechsel DA, Patel M. Mitochondria are a major source of paraquat-induced reactive oxygen species production in the brain. J Biol Chem 2007; 282(19):14186-93. Cerca con Google

Cha GH, Kim S, Park J, Lee E, Kim M, Lee SB, Kim JM, Chung J, Cho KS. Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila. Proc Natl Acad Sci U S A 2005; 102(29):10345-50. Cerca con Google

Chakraborty J, Basso V, Ziviani E. Post translational modification of Parkin. Biol Direct 2017; 12(1):6. Cerca con Google

Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Surmeier DJ. 'Rejuvenation' protects neurons in mouse models of Parkinson's disease. Nature 2007; 447(7148):1081-6. Cerca con Google

Chan H, Paur H, Vernon AC, Zabarsky V, Datla KP, Croucher MJ, Dexter DT. Neuroprotection and functional recovery associated with decreased microglial activation following selective activation of mGluR2/3 receptors in a rodent model of Parkinson's disease. Parkinsons Dis 2010; 2010. Cerca con Google

Chan NC, Salazar AM, Pham AH, Sweredoski MJ, Kolawa NJ, Graham RLJ, Hess S, Chan DC. Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum Mol Genet 2011; 20(9): 1726-1737. Cerca con Google

Chang S, Bray SM, Li Z, Zarnescu DC, He C, Jin P, Warren ST. Identification of small molecules rescuing fragile X syndrome phenotypes in Drosophila. Nat Chem Biol 2008; 4(4):256-63. Cerca con Google

Chaudhuri A, Bowling K, Funderburk C, Lawal H, Inamdar A, Wang Z, O'Donnell JM. Interaction of genetic and environmental factors in a Drosophila parkinsonism model. J Neurosci 2007; 27(10):2457-67. Cerca con Google

Chaudhuri KR, Healy DG, Schapira AH. Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol 2006; 5(3):235-45. Cerca con Google

Chen D, Gao F, Li B, Wang H, Xu Y, Zhu C, Wang G. Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. J Biol Chem 2010; 285(49):38214-23. Cerca con Google

Chen H, Chomyn A, Chan DC. Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem 2005; 280(28):26185-92. Cerca con Google

Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol. 2003; 160(2):189-200. Cerca con Google

Chen Y, Csordas G, Jowdy C, Schneider TG, Csordas N, Wang W, Liu Y, Kohlhaas M, Meiser M, Bergem S, Nerbonne JM, Dorn GW, Maack C. Mitofusin 2-containing mitochondrial-reticular microdomains direct rapid cardiomyocyte bioenergetic responses via interorganelle Ca(2+) crosstalk. Circ Res 2012; 111(7):863-75. Cerca con Google

Chiueh CC, Markey SP, Burns RS, Johannessen JN, Jacobowitz DM, Kopin IJ. Neurochemical and behavioral effects of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in rat, guinea pig, and monkey. Psychopharmacol Bull 1984; 20(3):548-53. Cerca con Google

Cipolat S, Martins de Brito O, Dal Zilio B, Scorrano L. OPA1 requires mitofusin 1 to promote mitochondrial fusion. Proc Natl Acad Sci U S A 2004; 101(45):15927-32 Cerca con Google

Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M. Drosophila pink1 is required for mitochondrial function and interacts genetically with Parkin. Nature 2006; 441(7097):1162-6. Cerca con Google

Cohen MM, Leboucher GP, Livnat-Levanon N, Glickman MH, Weissman AM. Ubiquitin-proteasome-dependent degradation of a mitofusin, a critical regulator of mitochondrial fusion. Mol Biol Cell 2008; 19(6):2457-64. Cerca con Google

Copeland DE, Dalton AJ. An association between mitochondria and the endoplasmic reticulum in cells of the pseudobranch gland of a teleost. J Biophys Biochem Cytol 1959; 5(3):393-6. Cerca con Google

Cosson P, Marchetti A, Ravazzola M, Orci L. Mitofusin-2 independent juxtaposition of endoplasmic reticulum and mitochondria: an ultrastructural study. PLoS One 2012; 7(9):e46293. Cerca con Google

Coulom H, Birman S. Chronic exposure to rotenone models sporadic Parkinson's disease in Drosophila melanogaster. J Neurosci 2004; 24:10993-98. Cerca con Google

Csordas G, Renken C, Varnai P, Walter L, Weaver D, Buttle KF, Balla T, Mannella CA, Hajnoczky G. Structural and functional features and significance of the physical linkage between ER and mitochondria. J Cell Biol 2006; 174(7):915-21. Cerca con Google

Csordas G, Varnai P, Golenar T, Roy S, Purkins G, Schneider TG, Balla T, Hajnoczky G. Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface. Mol Cell 2010; 39(1):121-32. Cerca con Google

Dauer W, Przedborski S. Parkinson's disease: Mechanisms and models. Neuron 2003; 39(6):889-909. Cerca con Google

Davis GC, Williams AC, Markey SP, Ebert MH, Caine ED, Reichert CM, Kopin IJ. Chronic Parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res 1979; 1(3):249-54. Cerca con Google

Day BJ, Patel M, Calavetta L, Chang LY, Stamler JS. A mechanism of paraquat toxicity involving nitric oxide synthase. Proc Natl Acad Sci U S A 1999; 96(22):12760-5. Cerca con Google

de Brito OM, Scorrano L. Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 2008; 456(7222):605-10. Cerca con Google

De Stefani D, Raffaello A, Teardo E, Szabò I, Rizzuto R. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 2011; 476(7360):336-40 Cerca con Google

De Vos KJ, Morotz GM, Stoica R, Tudor EL, Lau K-FF, Ackerley S, Warley A, Shaw CE, Miller CC. VAPB interacts with the mitochondrial protein PTPIP51 to regulate calcium homeostasis. Hum Mol Genet 2012; 21(6):1299-311. Cerca con Google

Deas E, Plun-Favreau H, Gandhi S, Desmond H, Kjaer S, Loh SH, Renton AE, Harvey RJ, Whitworth AJ, Martins LM, Abramov AY, Wood NW. PINK1 cleavage at position A103 by the mitochondrial protease PARL. Hum Mol Genet 2011; 20(5):867-79. Cerca con Google

Debattisti V, Pendin D, Ziviani E, Daga A, Scorrano L. Reduction of endoplasmic reticulum stress attenuates the defects caused by Drosophila mitofusin depletion. J Cell Biol. 2014; 204(3):303-12. Cerca con Google

Decressac M, Mattsson B, Bjorklund A. Comparison of the behavioural and histological characteristics of the 6-OHDA and alpha-synuclein rat models of Parkinson's disease. Exp Neurol 2012; 235(1):306-15. Cerca con Google

Del Dotto V, Mishra P, Vidoni S, Fogazza M, Maresca A, Caporali L, McCaffery JM, Cappelletti M, Baruffini E, Lenaers G, Chan D, Rugolo M, Carelli V, Zanna C. OPA1 Isoforms in the Hierarchical Organization of Mitochondrial Functions. Cell Rep 2017; 19(12):2557-2571. Cerca con Google

Delettre C, Griffoin JM, Kaplan J, Dollfus H, Lorenz B, Faivre L, Lenaers G, Belenguer P, Hamel CP. Mutation spectrum and splicing variants in the OPA1 gene. Hum Genet 2001; 109(6):584-91. Cerca con Google

Doss-Pepe EW, Chen L, Madura K. Alpha-synuclein and parkin contribute to the assembly of ubiquitin lysine 63-linked multiubiquitin chains. J Biol Chem 2005; 280(17):16619-24. Cerca con Google

Dove KK, Klevit RE. Structural Biology: Parkin's Serpentine Shape Revealed in the Year of the Snake. Curr Biol 2013; 23(16):R691-3. Cerca con Google

Durcan TM, Kontogiannea M, Bedard N, Wing SS, Fon EA. Ataxin-3 deubiquitination is coupled to Parkin ubiquitination via E2 ubiquitin-conjugating enzyme. J Biol Chem 2012; 287(1):531-41. Cerca con Google

Durcan TM, Kontogiannea M, Thorarinsdottir T, Fallon L, Williams AJ, Djarmati A, Fantaneanu T, Paulson HL, Fon EA. The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability. Hum Mol Genet 2011; 20(1):141-54. Cerca con Google

Ehringer H, Hornykiewicz O. Distribution of noradrenaline and dopamine (3-hydroxytyramine) in the human brain and their behavior in diseases of the extrapyramidal system. Klin Wochenschr 1960; 38:1236-9. Cerca con Google

Exner N, Treske B, Paquet D, Holmstrom K, Schiesling C, Gautier S, Carballo-Carbajal I, Berg D, Hoepken HH, Gasser T, Kruger R, Winklhofer KF, Vogel F, Reichert AS, Auburger G, Kahle PJ, Schmid B, Haass C. Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci 2007; 27(45):12413-8. Cerca con Google

Fabre E, Monserrat J, Herrero A, Barja G, Leret ML. Effect of MPTP on brain mitochondrial H2O2 and ATP production and on dopamine and DOPAC in the striatum. J Physiol Biochem 1999; 55(4):325-31. Cerca con Google

Fallon L, Belanger CM, Corera AT, Kontogiannea M, Regan-Klapisz E, Moreau F, Voortman J, Haber M, Rouleau G, Thorarinsdottir T, Brice A, van Bergen En Henegouwen PM, Fon EA. A regulated interaction with the UIM protein Eps15 implicates parkin in EGF receptor trafficking and PI(3)K-Akt signaling. Nat Cell Biol 2006; 8(8):834-42. Cerca con Google

Faull RL, Laverty R. Changes in dopamine levels in the corpus striatum following lesions in the substantia nigra. Exp Neurol 1969; 23(3):332-40. Cerca con Google

Feany MB, Bender WW. A Drosophila model of Parkinson's disease. Nature 2000; 404(6776):394-8. Cerca con Google

Fernagut PO, Hutson CB, Fleming SM, Tetreaut NA, Salcedo J, Masliah E, Chesselet MF. Behavioral and histopathological consequences of paraquat intoxication in mice: Effects of alpha-synuclein over-expression. Synapse 2007; 61(12):991-1001. Cerca con Google

Ferrante RJ, Schulz JB, Kowall NW, Beal MF. Systemic administration of rotenone produces selective damage in the striatum and globus pallidus, but not in the substantia nigra. Brain Res 1997; 753(1):157-62. Cerca con Google

Filadi R, Greotti E, Turacchio G, Luini A, Pozzan T, Pizzo P. Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling. Proc Natl Acad Sci U S A 2015; 112(17):E2174-81. Cerca con Google

Forno LS. Neuropathology of Parkinson's disease. J Neuropathol Exp Neurol 1996; 55(3):259-72. Cerca con Google

Fox SH. Non-dopaminergic treatments for motor control in Parkinson's disease. Drugs 2013; 73(13):1405-15. Cerca con Google

Frey TG, Mannella CA. The internal structure of mitochondria. Trends Biochem Sci 2000; 25(7):319-24. Cerca con Google

Friedman JR, Lackner LL, West M, DiBenedetto JR, Nunnari J, Voeltz GK. ER tubules mark sites of mitochondrial division. Science 2011; 334(6054):358-62. Cerca con Google

Friedman JR, Webster BM, Mastronarde DN, Verhey KJ, Voeltz GK. ER sliding dynamics and ER-mitochondrial contacts occur on acetylated microtubules. J Cell Biol 2010; 190(3):363-75. Cerca con Google

Gandhi PN, Chen SG, Wilson-Delfosse AL. Leucine-rich repeat kinase 2 (LRRK2): a key player in the pathogenesis of Parkinson's disease. J Neurosci Res 2009; 87(6):1283-95. Cerca con Google

Gandhi S, Muqit MM, Stanyer L, Healy DG, Abou-Sleiman PM, Hargreaves I, Heales S, Ganguly M, Parsons L, Lees AJ, Latchman DS, Holton JL, Wood NW, Revesz T. PINK1 protein in normal human brain and Parkinson's disease. Brain 2006; 129(Pt 7):1720-31. Cerca con Google

Gandre-Babbe S, van der Bliek AM. The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. Mol Biol Cell 2008; 19(6):2402-12. Cerca con Google

Gautier CA, Kitada T, Shen J. Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proc Natl Acad Sci U S A 2008; 105(32):11364-9. Cerca con Google

Gegg ME, Cooper JM, Chau KY, Rojo M, Schapira AH, Taanman JW. Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum Mol Genet 2010; 19(24):4861-70. Cerca con Google

Gegg ME, Cooper JM, Schapira AH, Taanman JW. Silencing of PINK1 expression affects mitochondrial DNA and oxidative phosphorylation in dopaminergic cells. PLoS One 2009; 4(3):e4756. Cerca con Google

Gehrke S, Wu Z, Klinkenberg M, Sun Y, Auburger G, Guo S, Lu B. PINK1 and Parkin Control Localized Translation of Respiratory Chain Component mRNAs on Mitochondria Outer Membrane. Cell Metab 2015; 21(1):95-108. Cerca con Google

Giasson BI, Murray IV, Trojanowski JQ, Lee VM. A hydrophobic stretch of 12 amino acid residues in the middle of a-synuclein is essential for filament assembly. J Biol Chem 2001; 276(4):2380-6. Cerca con Google

Gispert S, Ricciardi F, Kurz A, Azizov M, Hoepken HH, Becker D, Voos W, Leuner K, Muller WE, Kudin AP, Kunz WS, Zimmermann A, Roeper J, Wenzel D, Jendrach M, Garcia-Arencibia M, Fernandez-Ruiz J, Huber L, Rohrer H, Barrera M, Reichert AS, Rub U, Chen A, Nussbaum RL, Auburger G. Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. PLoS One 2009; 4(6):e5777. Cerca con Google

Glater EE, Megeath LJ, Stowers RS, Schwarz TL. Axonal transport of mitochondria requires milton to recruit kinesin heavy chain and is light chain independent. J Cell Biol 2006; 173(4):545-57. Cerca con Google

Glauser L, Sonnay S, Stafa K, Moore DJ. Parkin promotes the ubiquitination and degradation of the mitochondrial fusion factor mitofusin 1. J Neurochem 2011; 118(4):636-45. Cerca con Google

Goldberg MS, Fleming SM, Palacino JJ, Cepeda C, Lam HA, Bhatnagar A, Meloni EG, Wu N, Ackerson LC, Klapstein GJ, Gajendiran M, Roth BL, Chesselet MF, Maidment NT, Levine MS, Shen J. Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J Biol Chem 2003; 278(44):43628-35. Cerca con Google

Graham DG. Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 1978; 14(4):633-43. Cerca con Google

Greene AW, Grenier K, Aguileta MA, Muise S, Farazifard R, Haque ME, McBride HM, Park DS, Fon EA. Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment. EMBO Rep 2012; 13(4):378-85. Cerca con Google

Greene JC, Whitworth AJ, Kuo I, Andrews LA, Feany MB, Pallanck LJ. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci U S A 2003; 100(7):4078-83. Cerca con Google

Greggio E, Jain S, Kingsbury A, Bandopadhyay R, Lewis P, Kaganovich A, van der Brug MP, Beilina A, Blackinton J, Thomas KJ, Ahmad R, Miller DW, Kesavapany S, Singleton A, Lees A, Harvey RJ, Harvey K, Cookson MR. Kinase activity is required for the toxic effects of mutant LRRK2/dardarin, Neurobiol Dis. 2006; 23(2):329-41. Cerca con Google

Grice GL, Nathan JA. The recognition of ubiquitinated proteins by the proteasome. Cell Mol Life Sci 2016; 73(18):3497-506. Cerca con Google

Griffin EE, Graumann J, Chan DC. The WD40 protein Caf4p is a component of the mitochondrial fission machinery and recruits Dnm1p to mitochondria. J Cell Biol 2005; 170(2):237-48. Cerca con Google

Griparic L, van der Wel NN, Orozco IJ, Peters PJ, van der Bliek AM. Loss of the intermembrane space protein Mgm1/OPA1 induces swelling and localized constrictions along the lengths of mitochondria. J Biol Chem 2004; 279(18):18792-8. Cerca con Google

Gross O, Thomas CJ, Guarda G, Tschopp J. The inflammasome: an integrated view. Immunol Rev 2011; 243(1):136-51. Cerca con Google

Hales KG1, Fuller MT. Developmentally regulated mitochondrial fusion mediated by a conserved, novel, predicted GTPase. Cell 1997; 90(1):121-9. Cerca con Google

Halliday G, Herrero MT, Murphy K, McCann H, Ros-Bernal F, Barcia C, Mori H, Blesa FJ, Obeso JA. No Lewy pathology in monkeys with over 10 years of severe MPTP Parkinsonism. Mov Disord 2009; 24(10):1519-23. Cerca con Google

Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A, Fujita N, Oomori H, Noda T, Haraguchi T, Hiraoka Y, Amano A, Yoshimori T. Autophagosomes form at ER-mitochondria contact sites. Nature 2013; 495(7441):389-93. Cerca con Google

Hampe C, Ardila-Osorio H, Fournier M, Brice A, Corti O. Biochemical analysis of Parkinson's disease-causing variants of Parkin, an E3 ubiquitin-protein ligase with monoubiquitylation capacity. Hum Mol Genet 2006; 15(13):2059-75. Cerca con Google

Hantraye P, Brouillet E, Ferrante R, Palfi S, Dolan R, Matthews RT, Beal MF. Inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons. Nat Med 1996; 2(9):1017-21. Cerca con Google

Hantraye P, Varastet M, Peschanski M, Riche D, Cesaro P, Willer JC, Maziere M. Stable parkinsonian syndrome and uneven loss of striatal dopamine fibres following chronic MPTP administration in baboons. Neuroscience 1993; 53(1):169-78. Cerca con Google

Hasegawa E, Takeshige K, Oishi T, Murai Y, Minakami S. 1-Methyl-4-phenylpyridinium (MPP+) induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in bovine heart submitochondrial particles. Biochem Biophys Res Commun 1990; 170(3):1049-55. Cerca con Google

Healy DG, Falchi M, O'Sullivan SS, Bonifati V, Durr A, Bressman S, Brice A, Aasly J, Zabetian CP, Goldwurm S, Ferreira JJ, Tolosa E, Kay DM, Klein C, Williams DR, Marras C, Lang AE, Wszolek ZK, Berciano J, Schapira AH, Lynch T, Bhatia KP, Gasser T, Lees AJ, Wood NW. International LRRK2 Consortium. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study. Lancet Neurol 2008; 7(7):583-90. Cerca con Google

Heeman B, Van den Haute C, Aelvoet SA, Valsecchi F, Rodenburg RJ, Reumers V, Debyser Z, Callewaert G, Koopman WJ, Willems PH, Baekelandt V. Depletion of PINK1 affects mitochondrial metabolism, calcium homeostasis and energy maintenance. J Cell Sci 2011; 124(Pt 7):1115-25. Cerca con Google

Heikkila RE, Nicklas WJ, Vyas I, Duvoisin RC. Dopaminergic toxicity of rotenone and the MPTP ion after their stereotaxic administration to rats: Implication for the mechanism of MPTP toxicity. Neurosci Lett 1985; 62(3):389-94. Cerca con Google

Henn IH, Bouman L, Schlehe JS, Schlierf A, Schramm JE, Wegener E, Nakaso K, Culmsee C, Berninger B, Krappmann D, Tatzelt J, Winklhofer KF. Parkin mediates neuroprotection through activation of IkappaB kinase/nuclear factor-kappaB signaling. J Neurosci 2007; 27(8):1868-78. Cerca con Google

Hermann GJ, Thatcher JW, Mills JP, Hales KG, Fuller MT, Nunnari J, Shaw JM. Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p. J Cell Biol 1998; 143(2):359-73. Cerca con Google

Hetz C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol. 2012; 13(2):89-102. Cerca con Google

Hicke L. Protein regulation by monoubiquitin. Nat Rev Mol Cell Biol 2001; 2(3):195-201. Cerca con Google

Hinkle KM, Yue M, Behrouz B, Dachsel JC, Lincoln SJ, Bowles EE, Beevers JE, Dugger B, Winner B, Prots I, Kent CB, Nishioka K, Lin WL, Dickson DW, Janus CJ, Farrer MJ, Melrose HL. LRRK2 knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors. Mol Neurodegener 2012; 7:25. Cerca con Google

Hirsch EC, Hunot S. Neuroinflammation in Parkinson's disease: A target for neuroprotection? Lancet Neurol 2009; 8(4):382-97. Cerca con Google

Hoglinger GU, Feger J, Prigent A, Michel PP, Parain K, Champy P, Ruberg M, Oertel WH, Hirsch EC. Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats. J Neurochem 2003; 84(3):491-502. Cerca con Google

Hornykiewicz O, Kish SJ. Biochemical pathophysiology of Parkinson's disease. Adv Neurol 1987; 45:19-34. Cerca con Google

Hwa JJ1, Hiller MA, Fuller MT, Santel A. Differential expression of the Drosophila mitofusin genes fuzzy onions (fzo) and dmfn. Mech Dev 2002; 116(1-2):213-6. Cerca con Google

Ilijic E, Guzman JN, Surmeier DJ. The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson's disease. Neurobiol Dis 2011; 43(2):364-71. Cerca con Google

Imai Y, Soda M, Takahashi R. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J Biol Chem 2000; 275(46):35661-4. Cerca con Google

Ishihara N, Eura Y, Mihara K. Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity. J Cell Sci 2004; 117(Pt 26):6535-46. Cerca con Google

Ishihara N, Nomura M, Jofuku A, Kato H, Suzuki SO, Masuda K, Otera H, Nakanishi Y, Nonaka I, Goto Y, Taguchi N, Morinaga H, Maeda M, Takayanagi R, Yokota S, Mihara K. Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice. Nat Cell Biol 2009; 11(8):958-66. Cerca con Google

Iwasawa R, Mahul-Mellier AL, Datler C, Pazarentzos E, Grimm S. Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for apoptosis induction. EMBO J. 2011; 30(3):556-68. Cerca con Google

Jain S. Multi-organ autonomic dysfunction in Parkinson disease. Parkinsonism Relat Disord 2011; 17(2):77-83. Cerca con Google

Jankovic J. Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 2008; 79(4):368-376. Cerca con Google

Javitch JA, D'Amato RJ, Strittmatter SM, Snyder SH. Parkinsonism-inducing neurotoxin, N-methyl-4 phenyl-1,2,3,6-tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci U S A 1985; 82(7):2173-7. Cerca con Google

Jeon BS, Jackson-Lewis V, Burke RE. 6-hydroxydopamine lesion of the rat substantia nigra: Time course and morphology of cell death. Neurodegeneration 1995; 4(2):131-7. Cerca con Google

Jiang H, Jackson-Lewis V, Muthane U, Dollison A, Ferreira M, Espinosa A, Parsons B, Przedborski S. Adenosine receptor antagonists potentiate dopamine receptor agonist-induced rotational behavior in 6-hydroxydopamine-lesioned rats. Brain Res 1993; 613(2):347-51. Cerca con Google

Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ. Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J Cell Biol 2010; 191(5):933-42. Cerca con Google

Joch M, Ase AR, Chen CX, MacDonald PA, Kontogiannea M, Corera AT, Brice A, Seguela P, Fon EA. Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channels. Mol Biol Cell 2007; 18(8):3105-18. Cerca con Google

John GB, Shang Y, Li L, Renken C, Mannella CA, Selker JM, Rangell L, Bennett MJ, Zha J. The mitochondrial inner membrane protein mitofilin controls cristae morphology. Mol Biol Cell 2005; 16(3):1543-54. Cerca con Google

Kasten M, Klein C. The many faces of alpha-synuclein mutations. Mov Disord. 2013; 28(6):697-701. Cerca con Google

Kazlauskaite A, Martinez-Torres RJ, Wilkie S, Kumar A, Peltier J, Gonzalez A, Johnson C, Zhang J, Hope AG, Peggie M, Trost M, van Aalten DM, Alessi DR, Prescott AR, Knebel A, Walden H, Muqit MM. Binding to serine 65-phosphorylated ubiquitin primes Parkin for optimal PINK1-dependent phosphorylation and activation. EMBO Rep 2015; 16(8):939-54. Cerca con Google

Kendall JM, Sala-Newby G, Ghalaut V, Dormer RL, Campbell AK. Engineering the CA(2+)-activated photoprotein aequorin with reduced affinity for calcium. Biochem Biophys Res Commun 1992; 187(2):1091-7. Cerca con Google

Kilarski LL, Pearson JP, Newsway V, Majounie E, Knipe MD, Misbahuddin A, Chinnery PF, Burn DJ, Clarke CE, Marion MH, Lewthwaite AJ, Nicholl DJ, Wood NW, Morrison KE, Williams-Gray CH, Evans JR, Sawcer SJ, Barker RA, Wickremaratchi MM, Ben-Shlomo Y, Williams NM, Morris HR. Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease. Mov Disord 2012; 27(12):1522-9. Cerca con Google

Kim SJ, Park YJ, Hwang IY, Youdim MB, Park KS, Oh YJ. Nuclear translocation of DJ-1 during oxidative stress-induced neuronal cell death. Free Radic Biol Med 2012; 53(4):936-50. Cerca con Google

Kim Y, Park J, Kim S, Song S, Kwon SK, Lee SH, Kitada T, Kim JM, Chung J. PINK1 controls mitochondrial localization of Parkin through direct phosphorylation. Biochem Biophys Res Commun 2008; 377(3):975-80. Cerca con Google

Kirichok Y, Krapivinsky G, Clapham DE. The mitochondrial calcium uniporter is a highly selective ion channel. Nature 2004; 427(6972):360-4. Cerca con Google

Kirik D, Rosenblad C, Burger C, Lundberg C, Johansen TE, Muzyczka N, Mandel RJ, Bjorklund A. Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system. J Neurosci 2002; 22(7):2780-91. Cerca con Google

Klein RL, King MA, Hamby ME, Meyer EM. Dopaminergic cell loss induced by human A30P alpha-synuclein gene transfer to the rat substantia nigra. Hum Gene Ther 2002; 13(5):605-12. Cerca con Google

Kondapalli C, Kazlauskaite A, Zhang N, Woodroof HI, Campbell DG, Gourlay R, Burchell L, Walden H, Macartney TJ, Deak M, Knebel A, Alessi DR, Muqit MM. PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol 2012; 2(5):120080. Cerca con Google

Koob S, Reichert AS. Novel intracellular functions of apolipoproteins: the ApoO protein family as constituents of the Mitofilin/MINOS complex determines cristae morphology in mitochondria. Biol Chem 2014; 395(3):285-96. Cerca con Google

Kornmann B, Currie E, Collins SR, Schuldiner M, Nunnari J, Weissman JS, Walter P. An ER-mitochondria Tethering complex revealed by a synthetic biology screen. Science 2009; 325(5939):477-81. Cerca con Google

Kornmann B, Osman C, Walter P. The conserved GTPase Gem1 regulates endoplasmic reticulum-mitochondria connections. Proc Natl Acad Sci U S A 2011; 108(34):14151-6. Cerca con Google

Koshiba T, Detmer SA, Kaiser JT, Chen H, McCaffery JM, Chan DC. Structural basis of mitochondrial tethering by mitofusin complexes. Science 2004; 305(5685):858-62. Cerca con Google

Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M, Kimura Y, Tsuchiya H, Yoshihara H, Hirokawa T, Endo T, Fon EA, Trempe JF, Saeki Y, Tanaka K, Matsuda N. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 2014; 510(7503):162-6. Cerca con Google

Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev 2007; 87(1):99-163. Cerca con Google

Krols M, van Isterdael G, Asselbergh B, Kremer A, Lippens S, Timmerman V, Janssens S. Mitochondria associated membranes as hubs for neurodegeneration. Acta Neuropathol 2016; 131(4):505-23. Cerca con Google

Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, Kosel S, Przuntek H, Epplen JT, Schols L, Riess O. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet 1998; 18(2):106-8. Cerca con Google

Kupsky WJ, Grimes MM, Sweeting J, Bertsch R, Cote LJ. Parkinson's disease and megacolon: Concentric hyaline inclusions (Lewy bodies) in enteric ganglion cells. Neurology 1987; 37(7):1253-5. Cerca con Google

Lane N, Martin W. The energetics of genome complexity. Nature 2010; 467(7318):929-34. Cerca con Google

Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983; 219(4587):979-80. Cerca con Google

Langston JW, Irwin I, Langston EB, Forno LS. 1-Methyl-4-phenylpyridinium ion (MPP+): identification of a metabolite of MPTP, a toxin selective to the substantia nigra. Neurosci Lett 1984; 48(1):87-92. Cerca con Google

Langston JW. The Parkinson's complex: parkinsonism is just the tip of the iceberg. Ann Neurol 2006; 59(4):591-6. Cerca con Google

Lavara-Culebras E, Paricio N. Drosophila DJ-1 mutants are sensitive to oxidative stress and show reduced lifespan and motor deficits. Gene 2007; 400(1-2):158-65. Cerca con Google

Lev N, Ickowicz D, Melamed E, Offen D. Oxidative insults induce DJ-1 upregulation and redistribution: implications for neuroprotection. Neurotoxicology 2008; 29(3):397-405. Cerca con Google

Lev N, Roncevic D, Ickowicz D, Melamed E, Offen D. Role of DJ-1 in Parkinson's disease. J Mol Neurosci 2006; 29(3):215-25. Cerca con Google

Li HM, Niki T, Taira T, Iguchi-Ariga SM, Ariga H. Association of DJ-1 with chaperones and enhanced association and colocalization with mitochondrial Hsp70 by oxidative stress. Free Radic Res 2005; 39(10):1091-9. Cerca con Google

Lim KL, Chew KC, Tan JM, Wang C, Chung KK, Zhang Y, Tanaka Y, Smith W, Engelender S, Ross CA, Dawson VL, Dawson TM. Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formation. J Neurosci 2005; 25(8):2002-9. Cerca con Google

Lin W1, Kang UJ. Characterization of PINK1 processing, stability, and subcellular localization. J Neurochem 2008; 106(1):464-74. Cerca con Google

Lin X, Parisiadou L, Gu XL, Wang L, Shim H, Sun L, Xie C, Long CX, Yang WJ, Ding J, Chen ZZ, Gallant PE, Tao-Cheng JH, Rudow G, Troncoso JC, Liu Z, Li Z, Cai H. Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant alpha-synuclein. Neuron 2009; 64(6):807-27. Cerca con Google

Lo Bianco C, Ridet JL, Schneider BL, Deglon N, Aebischer P. alpha-Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson's disease. Proc Natl Acad Sci U S A 2002; 99(16):10813-8. Cerca con Google

Loson OC, Song Z, Chen H, Chan DC. Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Mol Biol Cell 2013; 24(5):659-67. Cerca con Google

Lu XH, Fleming SM, Meurers B, Ackerson LC, Mortazavi F, Lo V, Hernandez D, Sulzer D, Jackson GR, Maidment NT, Chesselet MF, Yang XW. Bacterial artificial chromosome transgenic mice expressing a truncated mutant parkin exhibit age-dependent hypokinetic motor deficits, dopaminergic neuron degeneration, and accumulation of proteinase K-resistant alpha-synuclein. J Neurosci 2009; 29(7):1962-76. Cerca con Google

Luthman J, Fredriksson A, Sundstrom E, Jonsson G, Archer T. Selective lesion of central dopamine or noradrenaline neuron systems in the neonatal rat: Motor behavior and monoamine alterations at adult stage. Behav Brain Res 1989; 33(3):267-77. Cerca con Google

Magerkurth C, Schnitzer R, Braune S. Symptoms of autonomic failure in Parkinson's disease: prevalence and impact on daily life. Clin Auton Res 2005; 15(2):76-82. Cerca con Google

Mak SK, McCormack AL, Manning-Bog AB, Cuervo AM, Di Monte DA. Lysosomal degradation of alpha-synuclein in vivo. J Biol Chem 2010; 285(18):13621-9. Cerca con Google

Malhotra JD, Kaufman RJ. The endoplasmic reticulum and the unfolded protein response. Semin Cell Dev Biol 2007; 18(6):716-31. Cerca con Google

Mannella CA, Marko M, Penczek P, Barnard D, Frank J. The internal compartmentation of rat-liver mitochondria: tomographic study using the high-voltage transmission electron microscope. Micros Res Tech 1994; 27(4):278-83. Cerca con Google

Manning-Bog AB, McCormack AL, Li J, Uversky VN, Fink AL, Di Monte DA. The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: Paraquat and alpha-synuclein. J Biol Chem 2002; 277(3):1641-4. Cerca con Google

Marder K, Wang Y, Alcalay RN, Mejia-Santana H, Tang MX, Lee A, Raymond D, Mirelman A, Saunders-Pullman R, Clark L, Ozelius L, Orr-Urtreger A, Giladi N, Bressman S. LRRK2 Ashkenazi Jewish Consortium. Age-specific penetrance of LRRK2 G2019S in the Michael J. Fox Ashkenazi Jewish LRRK2 Consortium. Neurology 2015; 85(1):89-95. Cerca con Google

Markopoulou K, Larsen KW, Wszolek EK, Denson MA, Lang AE, Pfeiffer RF, Wszolek ZK. Olfactory dysfunction in familial parkinsonism. Neurology 1997; 49(5):1262-7. Cerca con Google

Marsden CD. Neuromelanin and parkinson's disease. J Neural Transm Suppl 1983 ;19:121-41. Cerca con Google

Martin I, Dawson VL, Dawson TM. The impact of genetic research on our understanding of Parkinson's disease. Prog Brain Res 2010; 183:21-41. Cerca con Google

Mata IF, Wedemeyer WJ, Farrer MJ, Taylor JP, Gallo KA. LRRK2 in Parkinson's disease: protein domains and functional insights. Trends Neurosci 2006; 29(5):286-93. Cerca con Google

Matsuda N, Kitami T, Suzuki T, Mizuno Y, Hattori N, Tanaka K. Diverse effects of pathogenic mutations of Parkin that catalyze multiple monoubiquitylation in vitro. J Biol Chem 2006; 281(6):3204-9. Cerca con Google

Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA, Sou YS, Saiki S, Kawajiri S, Sato F, Kimura M, Komatsu M, Hattori N, Tanaka K. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol 2010; 189(2):211-21. Cerca con Google

McCormack AL, Thiruchelvam M, Manning-Bog AB, Thiffault C, Langston JW, Cory-Slechta DA, Di Monte DA. Environmental risk factors and Parkinson's disease: Selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis 2002; 10(2):119-27. Cerca con Google

McCormack JG, Denton RM. Role of calcium ions in the regulation of intramitochondrial metabolism. Properties of the Ca2+-sensitive dehydrogenases within intact uncoupled mitochondria from the white and brown adipose tissue of the rat. Biochem J 1980; 190(1):95-105. Cerca con Google

Mears JA, Lackner LL, Fang S, Ingerman E, Nunnari J, Hinshaw JE. Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission. Nat Struct Mol Biol 2011; 18(1):20-6. Cerca con Google

Meissner C, Lorenz H, Weihofen A, Selkoe DJ, Lemberg MK. The mitochondrial intramembrane protease PARL cleaves human Pink1 to regulate Pink1 trafficking. J Neurochem 2011; 117(5):856-67. Cerca con Google

Menzies FM, Yenisetti SC, Min KT. Roles of Drosophila DJ-1 in survival of dopaminergic neurons and oxidative stress. Curr Biol 2005; 15(17):1578-82. Cerca con Google

Messerschmitt M, Jakobs S, Vogel F, Fritz S, Dimmer KS, Neupert W, Westermann B. The inner membrane protein Mdm33 controls mitochondrial morphology in yeast. J Cell Biol 2003; 160(4):553-64. Cerca con Google

Meulener M, Whitworth AJ, Armstrong-Gold CE, Rizzu P, Heutink P, Wes PD, Pallanck LJ, Bonini NM. Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease. Curr Biol 2005; 15(17):1572-7. Cerca con Google

Mizuno Y, Sone N, Saitoh T. Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridinium ion on activities of the enzymes in the electron transport system in mouse brain. J Neurochem 1987; 48(6):1787-93. Cerca con Google

Moore DJ, West AB, Dikeman DA, Dawson VL, Dawson TM. Parkin mediates the degradation-independent ubiquitination of Hsp70. J Neurochem 2008; 105(5):1806-19. Cerca con Google

Moore DJ. Parkin: a multifaceted ubiquitin ligase. Biochem Soc Trans 2006; 34(Pt 5):749-53. Cerca con Google

Morais VA, Verstreken P, Roethig A, Smet J, Snellinx A, Vanbrabant M, Haddad D, Frezza C, Mandemakers W, Vogt-Weisenhorn D, Van Coster R, Wurst W, Scorrano L, De Strooper B. Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function. EMBO Mol Med 2009; 1(2):99-111. Cerca con Google

Muller-Rischart AK, Pilsl A, Beaudette P, Patra M, Hadian K, Funke M, Peis R, Deinlein A, Schweimer C, Kuhn PH, Lichtenthaler SF, Motori E, Hrelia S, Wurst W, Trumbach D, Langer T, Krappmann D, Dittmar G, Tatzelt J, Winklhofer KF. The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO. Mol Cell 2013; 49(5):908-21. Cerca con Google

Munoz JP, Ivanova S, Sanchez-Wandelmer J, Martinez-Cristobal P, Noguera E, Sancho A, Diaz-Ramos A, Hernandez-Alvarez MI, Sebast¡an D, Mauvezin C, Palacin M, Zorzano A. Mfn2 modulates the UPR and mitochondrial function via repression of PERK. EMBO J 2013; 32(17):2348-61. Cerca con Google

Naon D, Zaninello M, Giacomello M, Varanita T, Grespi F, Lakshminaranayan S, Serafini A, Semenzato M, Herkenne S, Hernandez-Alvarez MI, Zorzano A, De Stefani D, Dorn GW, Scorrano L. Critical reappraisal confirms that Mitofusin 2 is an endoplasmic reticulum-mitochondria tether. Proc Natl Acad Sci U S A 2016; 113(40):11249-11254. Cerca con Google

Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 2008; 183(5): 795-803. Cerca con Google

Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 2010; 8(1):e1000298. Cerca con Google

Newton K, Matsumoto ML, Wertz IE, Kirkpatrick DS, Lill JR, Tan J, Dugger D, Gordon N, Sidhu SS, Fellouse FA, Komuves L, French DM, Ferrando RE, Lam C, Compaan D, Yu C, Bosanac I, Hymowitz SG, Kelley RF, Dixit VM. Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies. Cell 2008; 134(4):668-78. Cerca con Google

Nicklas WJ, Vyas I, Heikkila RE. Inhibition of NADH-linked oxidation in brain mitochondria by MPP+, a metabolite of the neurotoxin MPTP. Life Sci 1985; 36(26):2503-8. Cerca con Google

Olichon A, Emorine LJ, Descoins E, Pelloquin L, Brichese L, Gas N, Guillou E, Delettre C, Valette A, Hamel CP, Ducommun B, Lenaers G, Belenguer P. The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space. FEBS Lett 2002; 523(1-3):171-6. Cerca con Google

Olzmann JA, Brown K, Wilkinson KD, Rees HD, Huai Q, Ke H, Levey AI, Li L, Chin LS. Familial Parkinson's disease-associated L166P mutation disrupts DJ-1 protein folding and function. J Biol Chem 2004; 279(9):8506-15. Cerca con Google

Ottolini D, Calì T, Negro A, Brini M. The Parkinson disease related protein DJ-1 counteracts mitochondrial impairment induced by the tumor suppressor protein p53 by enhancing endoplasmic reticulum-mitochondria tethering. Hum Mol Genet 2013; 22(11):2152-68. Cerca con Google

Paillusson S, Stoica R, Gomez-Suaga P, Lau DH, Mueller S, Miller T, Miller CC. There's Something Wrong With my MAM; the ER-Mitochondria Axis And Neurodegenerative Diseases. Trends Neurosci 2016; 39(3):146-57. Cerca con Google

Palade G. The fine structure of mitochondria. Anat Rec 1952; 114:427-51. Cerca con Google

Pankratz N, Pauciulo MW, Elsaesser VE, Marek DK, Halter CA, Wojcieszek J, Rudolph A, Shults CW, Foroud T, Nichols WC. Mutations in DJ-1 are rare in familial Parkinson disease. Neurosci Lett 2006; 408(3):209-13. Cerca con Google

Panov AV, Gutekunst CA, Leavitt BR, Hayden MR, Burke JR, Strittmatter WJ, Greenamyre JT. Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat Neurosci 2002; 5(8):731-6. Cerca con Google

Park CW, Ryu KY. Cellular ubiquitin pool dynamics and homeostasis. BMB Rep 2014; 47(9):475-82. Cerca con Google

Park J, Kim SY, Cha GH, Lee SB, Kim S, Chung J. Drosophila DJ-1 mutants show oxidative stress-sensitive locomotive dysfunction. Gene 2005; 361:133-9. Cerca con Google

Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, Bae E, Kim J, Shong M, Kim JM, Chung J. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 2006; 441(7097):1157-61. Cerca con Google

Parkinson J. An essay on the shaking palsy. 1817. J Neuropsychiatry Clin Neurosci 2002; 14(2):223-36; discussion 222. Cerca con Google

Perkins G, Young S, Renken C, Song JY, Lamont S, Martone M, Lindsey S, Frey T, Ellisman M. Electron tomography of large, multicomponent biological structures. J Struct Biol 1997; 120(3):219-27. Cerca con Google

Pesah Y, Pham T, Burgess H, Middlebrooks B, Verstreken P, Zhou Y, Harding M, Bellen H, Mardon G. Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress. Development 2004; 131(9):2183-94. Cerca con Google

Petit A, Kawarai T, Paitel E, Sanjo N, Maj M, Scheid M, Chen F, Gu Y, Hasegawa H, Salehi-Rad S, Wang L, Rogaeva E, Fraser P, Robinson B, St George-Hyslop P, Tandon A. Wild-type PINK1 prevents basal and induced neuronal apoptosis, a protective effect abrogated by Parkinson disease-related mutations. J Biol Chem 2005; 280(40):34025-32. Cerca con Google

Pickart CM, Eddins MJ. Ubiquitin: structures, functions, mechanisms. Biochim Biophys Acta 2004; 1695(1-3):55-72. Cerca con Google

Plun-Favreau H, Klupsch K, Moisoi N, Gandhi S, Kjaer S, Frith D, Harvey K, Deas E, Harvey RJ, McDonald N, Wood NW, Martins LM, Downward J. The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1. Nat Cell Biol 2007; 9(11):1243-52. Cerca con Google

Pogson JH, Ivatt RM, Sanchez-Martinez A, Tufi R, Wilson E, Mortiboys H, Whitworth AJ. The complex I subunit NDUFA10 selectively rescues Drosophila pink1 mutants through a mechanism independent of mitophagy. PLoS Genet 2014; 10(11):e1004815. Cerca con Google

Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL. Mutation in the a-synuclein gene identified in families with Parkinson's disease. Science 1997; 276(5321):2045-7. Cerca con Google

Poole AC, Thomas RE, Andrews LA, McBride HM, Whitworth AJ, Pallanck LJ. The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A 2008; 105(5):1638-43. Cerca con Google

Poole AC, Thomas RE, Yu S, Vincow ES, Pallanck L. The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/parkin pathway. PLoS One 2010; 5(4):e10054. Cerca con Google

Przedborski S, Ischiropoulos H. Reactive oxygen and nitrogen species: weapons of neuronal destruction in models of Parkinson's disease. Antioxid Redox Signal 2005; 7(5-6):685-93. Cerca con Google

Przedborski S, Jackson-Lewis V, Yokoyama R, Shibata T, Dawson VL, Dawson TM. Role of neuronal nitric oxide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity. Proc Natl Acad Sci U S A 1996; 93(10):4565-71. Cerca con Google

Rakovic A, Grunewald A, Kottwitz J, Bruggemann N, Pramstaller PP, Lohmann K, Klein C. Mutations in PINK1 and Parkin impair ubiquitination of Mitofusins in human fibroblasts. PLoS One 2011; 6(3):e16746. Cerca con Google

Ramonet D, Daher JP, Lin BM, Stafa K, Kim J, Banerjee R, Westerlund M, Pletnikova O, Glauser L, Yang L, Liu Y, Swing DA, Beal MF, Troncoso JC, McCaffery JM, Jenkins NA, Copeland NG, Galter D, Thomas B, Lee MK, Dawson TM, Dawson VL, Moore DJ. Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2. PLoS One 2011; 6(4):e18568. Cerca con Google

Rapizzi E, Pinton P, Szabadkai G, Wieckowski MR, Vandecasteele G, Baird G, Tuft RA, Fogarty KE, Rizzuto R. Recombinant expression of the voltage-dependent anion channel enhances the transfer of Ca2+ microdomains to mitochondria. J Cell Biol 2002; 159(4):613-24. Cerca con Google

Requejo-Aguilar R, Lopez-Fabuel I, Fernandez E, Martins LM, Almeida A, Bolanos JP. PINK1 deficiency sustains cell proliferation by reprogramming glucose metabolism through HIF1. Nat Commun 2014; 5:4514. Cerca con Google

Rizzuto R, Pinton P, Carrington W, Fay FS, Fogarty KE, Lifshitz LM, Tuft RA, Pozzan T. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 1998; 280(5370):1763-6. Cerca con Google

Rojas-Charry L, Cookson MR, Nino A, Arboleda H, Arboleda G. Downregulation of Pink1 influences mitochondrial fusion-fission machinery and sensitizes to neurotoxins in dopaminergic cells. Neurotoxicology 2014; 44:140-8. Cerca con Google

Rojo M, Legros F, Chateau D, Lombes A. Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. J Cell Sci 2002; 115(Pt 8):1663-74. Cerca con Google

Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 2007; 8(7):519-29. Cerca con Google

Rousseaux MW, Marcogliese PC, Qu D, Hewitt SJ, Seang S, Kim RH, Slack RS, Schlossmacher MG, Lagace DC, Mak TW, Park DS. Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease. Proc Natl Acad Sci U S A 2012; 109(39):15918-23. Cerca con Google

Rowland AA, Voeltz GK. Endoplasmic reticulum-mitochondria contacts: function of the junction. Nat Rev Mol Cell Biol 2012;13(10):607-25. Cerca con Google

Rubin GM, Spradling AC. Genetic transformation of Drosophila with transposable element vectors. Science 1982; 218(4570):348-53. Cerca con Google

Sachs C, Jonsson G. Mechanisms of action of 6-hydroxydopamine. Biochem Pharmacol 1975; 24(1):1-8. Cerca con Google

Salmena L, Pandolfi PP. Changing venues for tumour suppression: balancing destruction and localization by monoubiquitylation. Nat Rev Cancer 2007; 7(6):409-13. Cerca con Google

Sandebring A, Dehvari N, Perez-Manso M, Thomas KJ, Karpilovski E, Cookson MR, Cowburn RF, Cedazo-Minguez A. Parkin deficiency disrupts calcium homeostasis by modulating phospholipase C signalling. FEBS J 2009; 276(18):5041-52. Cerca con Google

Saner A, Thoenen H. Model experiments on the molecular mechanism of action of 6-hydroxydopamine. Mol Pharmacol 1971; 7(2):147-54. Cerca con Google

Santel A, Fuller MT. Control of mitochondrial morphology by a human mitofusin. J Cell Sci 2001; 114(Pt 5):867-74. Cerca con Google

Saotome M, Safiulina D, Szabadkai G, Das S, Fransson A, Aspenstrom P, Rizzuto R, Hajnoczky G. Bidirectional Ca2+-dependent control of mitochondrial dynamics by the Miro GTPase. Proc Natl Acad Sci U S A 2008; 105(52):20728-33. Cerca con Google

Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW. Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature 2013; 496(7445):372-6. Cerca con Google

Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD. Mitochondrial complex I deficiency in Parkinson's disease. J Neurochem 1990; 54(3):823-7. Cerca con Google

Schnell JD, Hicke L. Non-traditional functions of ubiquitin and ubiquitin-binding proteins. J Biol Chem 2003 ;278(38):35857-60. Cerca con Google

Schrag A, Horsfall L, Walters K, Noyce A, Petersen I. Prediagnostic presentations of Parkinson's disease in primary care: a case-control study. Lancet Neurol. 2015; 14(1):57-64. Cerca con Google

Senoh S, Creveling CR, Udenfriend S, Witkop B. Chemical, enzymatic and metabolic studies on the mechanism of oxidation of dopamine. J Am Chem Soc 1959; 81 (23):6236-6240 Cerca con Google

Sherer TB, Kim JH, Betarbet R, Greenamyre JT. Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation. Exp Neurol 2003; 179(1):9-16. Cerca con Google

Shiba-Fukushima K, Imai Y, Yoshida S, Ishihama Y, Kanao T, Sato S, Hattori N. PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy. Sci Rep 2012; 2:1002. Cerca con Google

Shimizu K, Ohtaki K, Matsubara K, Aoyama K, Uezono T, Saito O, Suno M, Ogawa K, Hayase N, Kimura K, Shiono H. Carrier-mediated processes in blood-brain barrier penetration and neural uptake of paraquat. Brain Res 2001; 906(1-2):135-42. Cerca con Google

Shimoji M, Zhang L, Mandir AS, Dawson VL, Dawson TM. Absence of inclusion body formation in the MPTP mouse model of Parkinson's disease. Brain Res Mol Brain Res 2005; 134(1):103-8. Cerca con Google

Shintani T, Klionsky DJ. Autophagy in health and disease: a double-edged sword. Science 2004; 306(5698):990-5. Cerca con Google

Simmen T, Aslan JE, Blagoveshchenskaya AD, Thomas L, Wan L, Xiang Y, Feliciangeli SF, Hung CH, Crump CM, Thomas G. PACS-2 controls endoplasmic reticulum-mitochondria communication and Bid-mediated apoptosis. EMBO J. 2005; 24(4):717-29. Cerca con Google

Sjostrand FS. Electron microscopy of mitochondria and cytoplasmic double membranes. Nature 1953; 171:30-31. Cerca con Google

Smirnowa E, Shurland DL, Ryazantsev SN, van der Bliek AM. A human dynamin-related protein controls the distribution of mitochondria. J Cell Biol 1998; 143(2):351-8. Cerca con Google

Son SM, Byun J, Roh SE, Kim SJ, Mook-Jung I. Reduced IRE1 alpha mediates apoptotic cell death by disrupting calcium homeostasis via the InsP3 receptor. Cell Death Dis 2014; 5:e1188. Cerca con Google

Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature 1997; 388(6645):839-40. Cerca con Google

St Johnston D. The art and design of genetic screens: Drosophila melanogaster. Nat Rev Genet 2002; 3(3):176-88. Cerca con Google

Stoica R, De Vos KJ, Paillusson S, Mueller S, Sancho RM, Lau K-FF, Vizcay-Barrena G, Lin W-LL, Xu Y-FF, Lewis J, Dickson DW, Petrucelli L, Mitchell JC, Shaw CE, Miller CC. ER-mitochondria associations are regulated by the VAPB-PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43. Nat Commun 2014; 5:3996. Cerca con Google

Stone SJ, Vance JE. Phosphatidylserine synthase-1 and -2 are localized to mitochondria-associated membranes. J Biol Chem 2000; 275(44):34534-40. Cerca con Google

Strappazzon F, Nazio F, Corrado M, Cianfanelli V, Romagnoli A, Fimia GM, Campello S, Nardacci R, Piacentini M, Campanella M, Cecconi F. AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1. Cell Death Differ 2015; 22(3):419-32. Cerca con Google

Stroud DA, Oeljeklaus S, Wiese S, Bohnert M, Lewandrowski U, Sickmann A, Guiard B, van der Laan M, Warscheid B, Wiedemann N. Composition and topology of the endoplasmic reticulum-mitochondria encounter structure. J Mol Biol 2011; 413(4):743-50. Cerca con Google

Szabadkai G, Bianchi K, Varnai P, De Stefani D, Wieckowski MR, Cavagna D, Nagy AI, Balla T, Rizzuto R. Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J Cell Biol 2006; 175(6):901-11. Cerca con Google

Tan EK, Skipper LM. Pathogenic mutations in Parkinson disease. Hum Mutat 2007; 28(7):641-53. Cerca con Google

Tan KR, Rudolph U, Luscher C. Hooked on benzodiazepines: GABAA receptor subtypes and addiction. Trends Neurosci 2011; 34(4):188-97. Cerca con Google

Tanaka A, Cleland MM, Xu S, Narendra DP, Suen DF, Karbowski M, Youle RJ. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol 2010; 191(7):1367-80. Cerca con Google

Tao X, Tong L. Crystal structure of human DJ-1, a protein associated with early onset Parkinson's disease. J Biol Chem 2003; 278(33):31372-9. Cerca con Google

Tenno T, Fujiwara K, Tochio H, Iwai K, Morita EH, Hayashi H, Murata S, Hiroaki H, Sato M, Tanaka K, Shirakawa M. Structural basis for distinct roles of Lys63- and Lys48-linked polyubiquitin chains. Genes Cells 2004; 9(10):865-75. Cerca con Google

Thiruchelvam M, McCormack A, Richfield EK, Baggs RB, Tank AW, Di Monte DA, Cory-Slechta DA. Age-related irreversible progressive nigrostriatal dopaminergic neurotoxicity in the paraquat and maneb model of the Parkinson's disease phenotype. Eur J Neurosci 2003; 18(3):589-600. Cerca con Google

Thiruchelvam M, Richfield EK, Baggs RB, Tank AW, Cory-Slechta DA. The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: Implications for Parkinson's disease. J Neurosci 2000b; 20(24):9207-14. Cerca con Google

Thomas B, Beal MF. Parkinson's disease. Hum Mol Genet 2007; 16 Spec No. 2:R183-94. Cerca con Google

Tieu K. A guide to neurotoxic animal models of Parkinson's disease. Cold Spring Harb Perspect Med 2011; 1(1):a009316. Cerca con Google

Tieu Q, Nunnari J. Mdv1p is a WD repeat protein that interacts with the dynamin-related GTPase, Dnm1p, to trigger mitochondrial division. J Cell Biol 2000; 151(2):353-66. Cerca con Google

Tieu Q, Okreglak V, Naylor K, Nunnari J. The WD repeat protein, Mdv1p, functions as a molecular adaptor by interacting with Dnm1p and Fis1p during mitochondrial fission. J Cell Biol 2002; 58(3):445-52. Cerca con Google

Tondera D, Czauderna F, Paulick K, Schwarzer R, Kaufmann J, Santel A. The mitochondrial protein MTP18 contributes to mitochondrial fission in mammalian cells. J Cell Sci 2005; 118(Pt 14):3049-59. Cerca con Google

Tong Y, Yamaguchi H, Giaime E, Boyle S, Kopan R, Kelleher RJ 3rd, Shen J. Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged mice. Proc Natl Acad Sci U S A 2010; 107(21):9879-84. Cerca con Google

Ungerstedt U. 6-Hydroxydopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 1968; 5(1):107-10. Cerca con Google

Vagnoni A, Bullock SL. A simple method for imaging axonal transport in aging neurons using the adult Drosophila wing. Nat Protoc 2016; 11(9):1711-23. Cerca con Google

Van Rompuy AS, Lobbestael E, Van der Perren A, Van den Haute C, Baekelandt V. Long-term overexpression of human wild-type and T240R mutant Parkin in rat substantia nigra induces progressive dopaminergic neurodegeneration. J Neuropathol Exp Neurol 2014; 73(2):159-74. Cerca con Google

Vance JE. Phospholipid synthesis in a membrane fraction associated with mitochondria. J Biol Chem 1990; 265(13):7248-56. Cerca con Google

Varastet M, Riche D, Maziere M, Hantraye P. Chronic MPTP treatment reproduces in baboons the differential vulnerability of mesencephalic dopaminergic neurons observed in Parkinson's disease. Neuroscience 1994; 63(1):47-56. Cerca con Google

Varnai P, Balla A, Hunyady L, Balla T. Targeted expression of the inositol 1,4,5-triphosphate receptor (IP3R) ligand-binding domain releases Ca2+ via endogenous IP3R channels. Proc Natl Acad Sci U S A 2005; 102(22):7859-64. Cerca con Google

Venken KJ, Schulze KL, Haelterman NA, Pan H, He Y, Evans-Holm M, Carlson JW, Levis RW, Spradling AC, Hoskins RA, Bellen HJ. MiMIC: a highly versatile transposon insertion resource for engineering Drosophila melanogaster genes. Nat Methods 2011; 8(9):737-43. Cerca con Google

Verfaillie T, Rubio N, Garg AD, Bultynck G, Rizzuto R, Decuypere JP, Piette J, Linehan C, Gupta S, Samali A, Agostinis P. PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress. Cell Death Differ 2012; 19(11):1880-91. Cerca con Google

Vezoli J, Fifel K, Leviel V, Dehay C, Kennedy H, Cooper HM, Gronfier C, Procyk E. Early presymptomatic and long-term changes of rest activity cycles and cognitive behavior in a MPTP-monkey model of Parkinson's disease. PLoS One 2011; 6(8):e23952. Cerca con Google

Von Coelln R, Thomas B, Savitt JM, Lim KL, Sasaki M, Hess EJ, Dawson VL, Dawson TM. Loss of locus coeruleus neurons and reduced startle in parkin null mice. Proc Natl Acad Sci U S A 2004; 101(29):10744-9. Cerca con Google

Wang D, Qian L, Xiong H, Liu J, Neckameyer WS, Oldham S, Xia K, Wang J, Bodmer R, Zhang Z. Antioxidants protect PINK1-dependent dopaminergic neurons in Drosophila. Proc Natl Acad Sci U S A 2006; 103(36):13520-5. Cerca con Google

Wang X, Schwarz TL. The mechanism of Ca2+ -dependent regulation of kinesin-mediated mitochondrial motility. Cell 2009; 136(1):163-74. Cerca con Google

Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL, Selkoe D, Rice S, Steen J, LaVoie MJ, Schwarz TL. PINK1 and Parkin Target Miro for Phosphorylation and Degradation to Arrest Mitochondrial Motility. Cell 2011 Nov 11; 147(4):893-906. Cerca con Google

Waterham HR, Koster J, van Roermund CW, Mooyer PA, Wanders RJ, Leonard JV. A lethal defect of mitochondrial and peroxisomal fission. N Engl J Med 2007; 356(17):1736-41. Cerca con Google

Wauer T, Komander D. Structure of the human Parkin ligase domain in an autoinhibited state. EMBO J 2013; 32(15):2099-112. Cerca con Google

Weihofen A, Thomas KJ, Ostaszewski BL, Cookson MR, Selkoe DJ. Pink1 forms a multi-protein complex with Miro and Milton, linking Pink1 function to mitochondrial trafficking. Biochemistry 2009; 48(9):2045-52. Cerca con Google

West AB, Moore DJ, Biskup S, Bugayenko A, Smith WW, Ross CA, Dawson VL, Dawson TM. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci U S A 2005; 102(46):16842-7. Cerca con Google

Wilson MA, Collins JL, Hod Y, Ringe D, Petsko GA. The 1.1-A resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease. Proc Natl Acad Sci U S A 2003; 100(16):9256-61. Cerca con Google

Winklhofer KF, Haass C. Mitochondrial dysfunction in Parkinson's disease. Biochim Biophys Acta 2010; 1802(1):29-44. Cerca con Google

Wong ED, Wagner JA, Gorsich SW, McCaffery JM, Shaw JM, Nunnari JM. The dynamin-related GTPase, Mgm1p, is an intermembrane space protein required for maintenance of fusion competent mitochondria. J Cell Biol. 2000; 151(2):341-52. Cerca con Google

Wozniak MJ, Bola B, Brownhill K, Yang YC, Levakova V, Allan VJ. Role of kinesin-1 and cytoplasmic dynein in endoplasmic reticulum movement in VERO cells. J Cell Sci 2009; 122(Pt 12):1979-89. Cerca con Google

Xu G, Jaffrey SR. Proteomic identification of protein ubiquitination events. Biotechnol Genet Eng Rev 2013; 29:73-109. Cerca con Google

Yamaguchi R, Perkins G. Dynamics of mitochondrial structure during apoptosis and the enigma of Opa1. Biochim Biophys Acta 2009; 1787(8):963-72. Cerca con Google

Yang Y, Gehrke S, Imai Y, Huang Z, Ouyang Y, Wang JW, Yang L, Beal MF, Vogel H, Lu B. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused inactivation of Drosophila Pink1 is rescued by by Parkin. Proc Natl Acad Sci U S A 2006; 103(28):10793-8. Cerca con Google

Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, Ampuero I, Vidal L, Hoenicka J, Rodriguez O, Atares B, Llorens V, Gomez Tortosa E, del Ser T, Munoz DG, de Yebenes JG. The new mutation, E46K, of a-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 2004; 55(2):164-73. Cerca con Google

Zhang CW, Hang L, Yao TP, Lim KL. Parkin Regulation and Neurodegenerative Disorders. Front Aging Neurosci 2015; 7: 248. Cerca con Google

Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature 2011; 469(7329):221-5. Cerca con Google

Ziviani E, Tao RN, Whitworth AJ. Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci U S A 2010; 107(11):5018-23. Cerca con Google

Zuchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, Zappia M, Nelis E, Patitucci A, Senderek J, Parman Y, Evgrafov O, Jonghe PD, Takahashi Y, Tsuji S, Pericak-Vance MA, Quattrone A, Battaloglu E, Polyakov AV, Timmerman V, Schroder JM, Vance JM. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type2A. Nat Genet 2004; 36(5):449-51. Cerca con Google

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