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Da Re, C (2011) Drosophila melanogaster as a model to study mitochondrial diseases. [Tesi di dottorato]

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Abstract (inglese)

Human mitochondrial diseases known as mitochondrial encephalomyopathies affecting the oxidative phosphorylation (OXPHOS) system can result from a large number of different mutations, both in the nuclear genome or in the maternally inherited mitochondrial DNA (mtDNA). The manifestations of mitochondrial diseases are extremely diverse, including numerous symptoms of variable severity, affecting tissues highly dependent on mitochondrial energy, such as brain, muscle, heart, and the sensorineural epithelia. Moreover these disorders can appear early in life, in children or in young adults (Wallace et al. 1999).
We used Drosophila melanogaster as a model organism to study a number of different mitochondrial disorders. The main reasons why the fruit fly is considered a good model are several. It is small, easy to grow, it has a short life cycle and generation time, it has a large number of progeny and finally it has a small completed sequenced genome, (Adams et al. 2000), with a large number of orthologs to human genes.
In particular we employed Drosophila to characterize the molecular function of three different genes whose dysfunctions result in encephalomyopathies affecting the functionality of the mitochondrial respiratory chain at different levels. However, in Drosophila, mutations in these genes cause a common larval lethal phenotype.
Furthermore another gene characterized in the present work is involved in the maintenance of mitochondrial DNA (mtDNA). Structural alterations of the mitochondrial genome or decrease of its copy number have profound consequences on mitochondrial function and cause severe human diseases which ultimately, also lead to death (Spinazzola and Zeviani 2005).
These genes, and the pathologies deriving from their impairments, were studied in Drosophila with different approaches which follow a common general scheme. Firstly we emloyed an approach which would allow ubiquitous or tissue-specific gene knock down, produced by exploiting the yeast UAS/GAL4 binary system. Specific dsRNA allows the targeted silencing of the interesting gene which can be spatially and temporally modulated (Brand and Perrimon 1993). When possible, we adopted procedures to obtain a gene knock out model. Generation of knock out lines is now a well established method which involves the recombination between transgenic lines bearing insertional elements present within the fruit fly genome. It is rather straightforward to obtain genomic deletions through the combination of FRT bearing transgenes flanking the region of interest, in the presence of FLP recombinase (Parks et al. 2004). Furthermore, when possible, confirmation of the genetic specificity of the observed defects in the Drosophila models was obtained by implementing appropriate gene rescue strategies.

Abstract (italiano)

Le malattie di mitocondriali umane, note anche come encefalomiopatie mitocondriali, vanno ad agire sulla funzionalità della fosforilazione ossidativa (OXPHOS) e sono il risultato di un gran numero di mutazioni, che possono localizzarsi sia a livello del genoma nucleare sia a livello di quello mitocondriale (mtDNA a eredità materna). Le malattie mitocondriali producono sintomi estremamente diversi, di gravità variabile, che vanno a colpire tessuti ad elevata richiesta energetica, quali cervello, muscolo, cuore, ed epiteli sensorio-neurali. Inoltre questi disturbi possono apparire precocemente, in giovane età, nei bambini o in età adulta (Wallace et al. 1999).
In particolare si è utilizzato Drosophila melanogaster come un organismo modello per studiare varie malattie mitocondriali. Le principali ragioni che fanno del moscerino della frutta un ottimo organismo modello sono molteplici. Innanzitutto ha dimensioni ridotte, è facile da crescere, possiede ciclo di vita e tempo di generazione assai brevi, produce un buon numero di progenie ed è caratterizzato da un genoma piccolo completamente sequenziato, (Adams et al. 2000), con la presenza di gran numero di geni ortologhi a quelli umani.
In particolare, grazie all’utilizzo di Drosophila, sono stati analizzati, a livello molecolare, tre diversi geni, le cui disfunzioni danno luogo ad encefalomiopatie, che vanno a colpire la funzionalità della catena respiratoria mitocondriale a diversi livelli. Nel complesso mutazioni in questi geni causano un fenotipo letale. Inoltre, è stato caratterizzato anche un altro gene, coinvolto nella stabilità e nel mantenimento del genoma mitocondriale (mtDNA). Alterazioni strutturali dell’ mtDNA o decremento del numero di copie dello stesso, hanno profonde conseguenze sulla funzionalità mitocondriale e determinano l’insorgenza di gravi malattie umane, per la maggioranza letali (Spinazzola e Zeviani 2005).
Questi geni, e le patologie che derivano da un loro malfunzionamento, sono stati studiati in Drosophila con approcci diversi che tuttavia seguono un schema generale comune.
In primo luogo, la versatilità del nostro organismo modello rende possibile il silenziamento post-trascrizionale del gene in questione, sfruttando il sistema binario di lievito UAS-GAL4 (Brand e Perrimon 1993). In tal modo è possibile ottenere l’abbattimento del gene, abbattimento che può essere modulato sia temporalmente che spazialmente.
Inoltre, qualora le condizioni lo permettano, è di grande utilità la generazione di un modello knock out (KO) del gene. Il KO in drosophila è tuttora un metodo di facile generazione, che prevede un meccanismo di ricombinazione tra linee di drosophila contenenti elementi inserzionali localizzati alle estremità del gene da eliminare. In dettaglio il meccanismo descritto da (Parks et al. 2004) sfrutta la ricombinazione specifica tra siti FRT, localizzati all’interno dell’elemento trasponibile, in presenza di flippasi (FLP) che catalizza l’excisione del gene d’interesse.
Una volta eseguito il silenziamento post-trascrizionale o il KO del gene d’interesse, al fine di validare i modelli ottenuti, il passo successivo è quello che prevede il recupero del fenotipo osservato. Esperimenti di “rescue” prevedono la realizzazione di un costrutto contente il gene d’interesse sotto il controllo di uno specifico promotore, in grado di attivarne l’espressione in un contesto “loss of gene”. Se l'espressione del gene sintetico risulta in grado di recuperare il fenotipo KO/KD, la caratterizzazione genica è completata. Nello specifico, in questo lavoro è stato condotto lo studio di quattro diversi geni seguendo lo stesso schema comune, mirato a descrivere la funzione molecolare di questi geni coinvolti in devastanti sindromi mitocondriali.

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Tipo di EPrint:Tesi di dottorato
Relatore:Zordan, MA
Dottorato (corsi e scuole):Ciclo 23 > Scuole per il 23simo ciclo > BIOSCIENZE > GENETICA E BIOLOGIA MOLECOLARE DELLO SVILUPPO
Data di deposito della tesi:NON SPECIFICATO
Anno di Pubblicazione:27 Gennaio 2011
Parole chiave (italiano / inglese):Mitochondrial diseases/ Malattie mitocondriali, Drosophila melanogaster
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/18 Genetica
Struttura di riferimento:Dipartimenti > Dipartimento di Biologia
Codice ID:3467
Depositato il:19 Lug 2011 17:10
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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.

Agostino A, Invernizzi F, Tiveron C, Fagiolari G, Prelle A, Lamantea E, Giavazzi A, Battaglia G, Tatangelo L, Tiranti V, Zeviani M (2003). Constitutive knockout of Surf1 is associated with high embryonic lethality, mitochondrial disease and cytochrome c oxidase deficiency in mice. Hum Mol Genet, 12(4):399-413. Cerca con Google

Angelin A, Tiepolo T, Sabatelli P, Grumati P, Bergamin N, Golfieri C, Mattioli E, Gualandi F, Ferlini A, Merlini L, Maraldi NM, Bonaldo P and Bernardi P (2007). Mitochondrial dysfunction Cerca con Google

in the pathogenesis of Ullrich congenital muscular dystrophy and prospective therapy with cyclosporins. Proc Natl Acad Sci USA 104, 991–996. Cerca con Google

Aravind L (1999). An evolutionary classification of the metallo ß-lactamase fold proteins. In Silico Biol 1, 69–91. Cerca con Google

Arner ES and Eriksson S (1995). Mammalian deoxyribonucleoside kinases. Pharmacol Ther 67, 155–186. Cerca con Google

Arpaia E, Benveniste P, Di CA, Gu Y, Dalal I, Kelly S, Hershfield M, Pandolfi PP, Roifman CM and Cohen A (2000). Mitochondrial basis for immune deficiency. Evidence from purine Cerca con Google

nucleoside phosphorylase-deficient mice. J Exp Med 191, 2197–220.8. Cerca con Google

Attardi G, Schatz G (1988). Biogenesis of mitochondria. Annu Rev Cell Biol 4, 289–333. Cerca con Google

Barrientos A, Korr D, Tzagoloff A (2002). Shy1p is necessary for full expression of mitochondrial COX1 in the yeast model of Leigh's syndrome. EMBO J 21, (1-2):43-52. Cerca con Google

Berk AJ and Clayton DA (1973). A genetically distinct thymidine kinase in mammalian mitochondria. Exclusive labeling of mitochondrial deoxyribonucleic acid. J Biol Chem 248, Cerca con Google

2722–2729. Cerca con Google

Bianchi V, Pontis E and Reichard P (1987). Regulation of pyrimidine deoxyribonucleotide metabolism by substrate cycles in dCMP deaminasedeficient V79 hamster cells. Mol Cell Cerca con Google

Biol 7, 4218–4224. Cerca con Google

Blatch GL and Lassle M (1999). The tetratricopeptide repeat: a structural motif mediating protein-protein interactions. BioEssays 21, 932–939. Cerca con Google

Bogenhagen D and Clayton DA (1976). Thymidylate nucleotide supply for mitochondrial DNA synthesis in mouse L-cells. Effect of 5-fluorodeoxyuridine and methotrexate in thymidine kinase plus and thymidine kinase minus cells. J Biol Chem 251, 2938–2944. Cerca con Google

Bogenhagen D, Clayton DA (1974). The number of mitochondrial deoxyribonucleic acid genomes in mouse L and human HeLa cells. Quantitative isolation of mitochondrial Cerca con Google

deoxyribonucleic acid. J Biol Chem 49, 7991. Cerca con Google

Borst A, Haag J, Rieff DF (2010). Fly motion vision. Annu. Rev. Neurosci. 33, 49-70. Cerca con Google

Bourdon A, Minai L, Serre V, Jais JP, Sarzi E, Aubert S, Chretien D, de LP, Paquis-Flucklinger V, Arakawa H, Nakamura Y, Munnich A and Rotig A (2007). Mutation of RRM2B, encoding Cerca con Google

p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. Nat Genet 39, 776–780. Cerca con Google

Bradshaw HDJ and Deininger PL (1984). Human thymidine kinase gene: molecular cloning and nucleotide sequence of a cDNA expressible in mammalian cells. Mol. Cell. Biol. 4, 2316–2320. Cerca con Google

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

Brandt U, Yu L, Yu CA and Trumpower BL (1993). The mitochondrial targeting presequence of the Rieske iron–sulfur protein is processed in a single step after insertion into the cytochrome bc1 complex in mammals and retained as a subunit in the complex. J Bio Chem 268, 8387–8390. Cerca con Google

Bridges EG, Jiang Z and Cheng YC (1999). Characterization of a dCTP transport activity reconstituted from human mitochondria. J Biol Chem 274, 4620–4625. Cerca con Google

Bugiani M, Invernizzi F, Alberio S, Briem E, Lamantea E, Carrara F, Moroni I, Farina L., Spada M, and Donati MA (2004). Clinical and molecular findings in children with complex I deficiency. Biochim Biophys Acta 1659, 136-147. Cerca con Google

Burlina AB, Dionisi-Vici C, Bennet MJ, Gibson KM, Servidei S, Bertini E, Hale DE, Schimidt-Sommerfeld E, Sabetta G, Zacchello F, Rinaldo P (1994) A new syndrome with Cerca con Google

ethylmalonic aciduria and normal fatty acid oxidation in fibroblasts. J Pediatr 124, 79–86. Cerca con Google

Burlina AB, Zacchello F, Dionisi-Vici C, Bertini E, Sabetta G, Bennet MJ, Hale DE, Schimidt-Sommerfeld E, Rinaldo P (1991). New clinical phenotype of branched-chain acyl-CoA oxidation defect. Lancet 338, 1522–1523. Cerca con Google

Chabes A and Thelander L (2000). Controlled protein degradation regulates ribonucleotide reductase activity in proliferating mammalian cells during the normal Cerca con Google

cell cycle and in response to DNA damage and replication blocks. J Biol Chem 275, 17747–17753. Cerca con Google

Chomyn A (1996). In vivo labeling and analysis of human mitochondrial translation products. Methods Enzymol 264, 197–211. Cerca con Google

Coenen M, van den Heuvel LP, Nijtmans LG, Morava E, Marquardt I (1999). SURFEIT-1 gene analysis and twodimensional blue native gel electrophoresis in cytochrome Cerca con Google

coxidase deficiency. Biochem Biophys Res Commun 265, 339–344. Cerca con Google

Cohen A, Hirschhorn R, Horowitz SD, Rubinstein A, Polmar SH, Hong R and Martin DW, Jr. (1978). Deoxyadenosine triphosphate as a potentially toxic metabolite in adenosine Cerca con Google

deaminase deficiency. Proc Natl Acad Sci U S A 75, 472–476. Cerca con Google

Corydon MJ, Vockley J, Rinaldo P, Rhead WJ, Kjeldsen M, Winter V, Riggs C, Babovic-Vuksanovic D, Smeitink J, De Jong J, Levy H, Sewell AC, Roe C, Matern D, Dasouki M, Cerca con Google

Gregersen N (2001). Role of common variant alleles in the molecular basis of short-chain acyl-CoA dehydrogenase deficiency. Pediatr Res 49, 18–23. Cerca con Google

Cruciat CM, Hell K, Folsch H, Neupert W and Stuart RA (1999). Bcs1p, an AAA-family member, is a chaperone for the assembly of the cytochrome bc(1) complex. EMBO J 18, Cerca con Google

5226–5233. Cerca con Google

Dell'agnello C, Leo S, Agostino A, Szabadkai G, Tiveron C, Zulian A, Prelle A, Roubertoux P, Rizzuto R, Zeviani M (2007). Increased longevity and refractoriness to Ca(2+)- Cerca con Google

dependent neurodegeneration in Surf1 knockout mice. Hum Mol Genet 16(4), 431-44. Cerca con Google

Deng WB, Feng YP (1997). Effect of dilbutylphthaline on brain edema in rats subjected to focal cerebral ischemia. Chi Med Sci J 12, 102. Cerca con Google

Deng Y and Nicholson RA (2005). Block of electron transport by surangin B in bovine heart mitochondria. Pestic Bioch and Physiol 81 39–50 Cerca con Google

Dietzl G, Chen D, Schnorrer F, Su KC, Barinova Y, Fellner M, Gasser B, Kinsey K, Oppel S, Scheiblauer S, Couto A, Marra V, Keleman K and Dickson BJ (2007). A genome-wide Cerca con Google

transgenic RNAi library for conditional gene inactivation in Drosophila. Nature 448, 151–156. Cerca con Google

DiMauro S and Schon EA (2003). Mitochondrial respiratorychain diseases. New Engl J Med 348, 2656–2668. Cerca con Google

DiMauro S and Schon EA (2008). Mitochondrial Disorders in the Nervous System Annu Rev Neurosci 31, 91-123. Cerca con Google

DiMauro S, Moraes CT, Shanske S, Lombes A, Nakase H, Mita S, Tritschler HJ, Bonilla E, Miranda AF and Schon EA (1991). Anomalous intensity-dependent vibrational distributions of oxygen molecules in a nonresonant laser field: A molecular perspective. Rev Neurologiq 147, 443–449. Cerca con Google

DiMauro S, Zeviani M, Rizzuto R, Lombes A, Nakase H, Bonilla E, Miranda A and Schon E (1988). Molecular defects in cytochrome c oxidase in mitochondrial diseases. J Bioenerg Cerca con Google

Biomembr 20, 353–364. Cerca con Google

Dolce V, Fiermonte G, Runswick MJ, Palmieri F and Walker JE (2001). The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals. Proc Natl Acad Sci U S A 98, 2284–2288. Cerca con Google

Dougherty DA (1996). Cation-pi interactions in chemistry and biology: a new view of benzene, Phe, Tyr, and Trp. Science 271, 163–168. Cerca con Google

Drysdale RA, Crosby MA, The flybase consortium (2005). FlyBase: genes and gene models. Nucleic Acids Research 33, 390–395. Cerca con Google

Fadic R and Johns DR (1996). Clinical spectrum of mitochondrial diseases. Semin Neurol 16, 11–20. Cerca con Google

Farina L, Chiapparini L, Uziel G, Bugiani M and. Zeviani M (2002). MR findings in Leigh syndrome with COX deficiency and Surf-1 mutations. AJNR Am J Neuroradiol. 23, 1095–1100. Cerca con Google

Fergestad T, Bostwick B and Ganetzky B (2006). Metabolic disruption in Drosophila bangsensitive seizure mutants. Genetics 173,1357-1364. Cerca con Google

Fernandez-Ayala DJM, Sanz A, Vartiainen S, Kemppainen KK, Babusiak M, Mustalahti E, Costa R, Tuomela T, Zeviani M, Chung J, O'Dell KMC, Rustin P, Jacobs HT (2009). Expression of the Ciona intestinalis alternative oxidase (AOX) in Drosophila Cerca con Google

complements defects in mitochondrial oxidative phosphorylation. Cell Metab 9(5), 449–60. Cerca con Google

Fernandez-Vizarra E, Bugiani M, Goffrini P, Carrara F, Farina L, Procopio E, Donati A, Uziel G, Ferrero and Zeviani M. (2007). Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy. Hum. Mol. Genet. 16, 1241–1252. Cerca con Google

Ferraro P, Nicolosi L, Bernardi P, Reichard P and Bianchi V (2006). Mitochondrial deoxynucleotide pool sizes in mouse liver and evidence for a transport mechanism for thymidine monophosphate. Proc Natl Acad Sci U S A 103, 18586–18591. Cerca con Google

Ferraro P, Pontarin G, Crocco L, Fabris S, Reichard P and Bianchi V (2005). Mitochondrial deoxynucleotide pools in quiescent fibroblasts: a possible model for mitochondrial Cerca con Google

neurogastrointestinal encephalomyopathy (MNGIE). J Biol Chem 280, 24472–24480. Cerca con Google

Fiermonte G, De Leonardis F, Todisco S, Palmieri L, Lasorsa FM and Palmieri F (2004). Identification of the mitochondrial ATP-Mg/Pi transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution. J Biol Chem 279, 30722–30730. Cerca con Google

Floyd S, Favre C, Lasorsa FM, Leahy M, Trigiante G, Stroebel P, Marx A, Loughran G, O'Callaghan K, Marobbio CM, Slotboom DJ, Kunji ER, Palmieri F and O'Connor R (2007). Cerca con Google

The insulin-like growth factor-I-mTOR signaling pathway induces the mitochondrial pyrimidine nucleotide carrier to promote cell growth. Mol Biol Cell 18, 3545–3555. Cerca con Google

Fuller MT (1993). Spermatogenesis. In The Development of Drosophila, (M. Martinez-Arias and M. Bate, eds.) Cold Spring Harbor Press, Cold Spring Harbor, New York. pp.71-147. Cerca con Google

Garavaglia B, Colamaria V, Carrara F, Tonin P, Rimoldi M, Uziel G (1994). Muscle cytochrome c oxidase deficiency in two Italian patients with ethylmalonic aciduria and peculiar clinical phenotype. J Inher Metab Dis 17, 301–303. Cerca con Google

García-Silva MT, Campos Y, Ribes A, Briones P, Cabello A, Santos Borbujo J, Arenas J, Garavaglia B. (1994). Encephalopathy, petechiae, and acrocyanosis with ethylmalonic Cerca con Google

aciduria associated with muscle cytochrome c oxidase deficiency. J Pediatr 125, 843–844. Cerca con Google

Garcia-Silva MT, Ribes A, Campos Y, Garavaglia B, Arenas J (1997). Syndrome of encephalopathy, petechiae, and ethylmalonic aciduria. Pediatr Neurol 17, 165–170. Cerca con Google

Gazziola C, Ferraro P, Moras M, Reichard P and Bianchi V (2001). Cytosolic high k(M) 5’-nucleotidase and 5’(3’)-deoxyribonucleotidase in substrate cycles involved in nucleotide metabolism. J BiolChem 276, 6185–6190. Cerca con Google

Giansanti MG, Farkas RM, Bonaccorsi S, Lindsley DL, Wakimoto BT, Fuller MT and Gatti M (2004). Genetic dissection of meiotic cytokinesis in Drosophila males. Mol Biol Cell 15, 2509-2522. Cerca con Google

Glasscock E and Tanouye MA (2005). Drosophila couch potato mutants exhibit complex neurological abnormalities including epilepsy phenotypes. Genetics 169, 2137-2149. Cerca con Google

Gomes CM, Frazao C, Xavier AV, Legall J, Teixeira M (2002). Functional control of the binuclear metal site in the metallo-beta-lactamase-like fold by subtle amino acid replacements. Protein Science 11, 707–712. Cerca con Google

Gregersen N, Winter VS, Corydon MJ, Corydon TJ, Rinaldo P, Eiberg H (1998). Identification of four new mutations in the short-chain acyl-CoA dehydrogenase (SCAD) gene in two patients: one of the variant alleles, 511C-T, is present at an Cerca con Google

unexpectedly high frequency in the general population, as was the case for 625G-A, together conferring susceptibility to ethylmalonic aciduria. Hum Mol Genet 7, 619–627. Cerca con Google

Grosso, S, Mostardini R, Farnetani MA, Molinelli M, Berardi R, Dionisi-Vici C, Rizzo C, Morgese G, Balestri P (2002). Ethylmalonic encephalopathy, further clinical and neuroradiological characterization. J Neurol 249, 1446–1450. Cerca con Google

Gudz TI, Tserng KY, Hoppel CL (1997). Direct inhibition of mitochondrial respiratory chain complex III by cellpermeable ceramide, J. Biol. Chem. 272 24154–24158. Cerca con Google

Hakansson P, Hofer A and Thelander L (2006). Regulation of mammalian ribonucleotide reduction and dNTP pools after DNA damage and in resting cells. J Biol Chem 281, 7834–7841. Cerca con Google

Hanson BJ, Carrozzo R, Piemonte F, Tess A, Robinson BH (2001). Cytochrome c oxidasedeficient patients have distinct subunit assembly profiles. J Biol Chem 276, 16296–16301.9. Cerca con Google

Haslbrunner E, Tuppy H and Schatz G. (1964). Deoxyribonucleic Acid Associated with Yeast Mitochondria. Biochem Biophys Res Commun 15, 127–132. Cerca con Google

Heckmatt L and Dubowitz V (1984). Needle biopsy of skeletal muscle. Muscle Nerve 7, 594. Cerca con Google

Herrmann JM and Funes S (2005). Biogenesis of cytochrome oxidase-sophisticated assembly lines in the mitochondrial inner membrane. Gene (Amst) 354, 43–52. Cerca con Google

Higashitsuji H, Nagao T, Nonoguchi K, Fujii S, Itoh K, Fujita J (2002). A novel protein overexpressed in hepatoma accelerates export of NF-KB from the nucleus and inhibits p53-dependent apoptosis. Cancer Cell 2 ,335–346. Cerca con Google

Holmgren D, Wahlander H, Eriksson BO, Oldfors A, Holme E and Tulinius M (2003). Cardiomyopathy in children with mitochondrial disease, clinical course and cardiological findings. Eur Heart J 24, 280–288. Cerca con Google

Holt IJ, Harding AE, Morgan Hughes JA (1988). Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331, 717–719. Cerca con Google

Irwin WA, Bergamin N, Sabatelli P, Reggiani C, Megighian A, Merlini L, Braghetta P, Columbaro M, Volpin D, Bressan GM, Bernardi P and Bonaldo P (2003). Mitochondrial Cerca con Google

dysfunction and apoptosis in myopathic mice with collagen VI deficiency. Nat Genet 35, 267–271. Cerca con Google

Johansson M and Karlsson A (1997). Cloning of the cDNA and chromosome localization of the gene for human thymidine kinase 2. J Biol Chem 272, 8454–8458. Cerca con Google

Jordan A and Reichard P (1998). Ribonucleotide reductases. Annu Rev Biochem 67, 71–98. Cerca con Google

Kauffman MG and Kelly TJ (1991). Cell cycle regulation of thymidine kinase: residues near the carboxyl terminus are essential for the specific degradation of the enzyme at mitosis. Mol Cell Biol 11, 2538–2546. Cerca con Google

Kicska GA, Long L, Horig H, Fairchild C, Tyler PC, Furneaux RH, Schramm VL and Kaufman HL (2001). Immucillin H, a powerful transition-state analog inhibitor of purine nucleoside phosphorylase, selectively inhibits human T lymphocytes. Proc Natl Acad Sci U S A 98, 4593–4598. Cerca con Google

Kimmins S and MacRae TH (2000). Maturation of steroid receptors: an example of functional cooperation among molecular chaperones and their associated proteins. Cell Cerca con Google

Stress Chaperones 5, 76-86 Cerca con Google

Koeberl DD, Young SP, Gregersen NS, Vockley J, Smith WE, Benjamin DK Jr, An Y, Weavil SD, Chaing SH, Bali D, McDonald MT, Kishnani PS, Chen YT, Millington DS (2003). Rare disorders of metabolism with elevated butyryl- and isobutyrylcarnitine Cerca con Google

detected by tandem mass spectrometry newborn screening. Pediatr Res 54, 219–223. Cerca con Google

Kotarsky H., (2007). BCS1L is expressed in critical regions for neural development during ontogenesis in mice. Gene Expr. Patterns 7, 266-273 Cerca con Google

Kumar D, Gustafsson C, Klessig DF (2006). Validation of RNAi silencing specificity using synthetic genes: salicylic acid-binding protein 2 is required for innate immunity in plants. Plant J, 45(5):863-8. Cerca con Google

Kunji ER (2004). The role and structure of mitochondrial carriers. FEBS Lett 564, 239–244. Cerca con Google

Lam W, Chen C, Ruan S, Leung CH and Cheng YC (2005). Expression of deoxynucleotide carrier is not associated with the mitochondrial DNA depletion caused by anti-HIV Cerca con Google

dideoxynucleoside analogs and mitochondrial dNTP uptake. Mol Pharmacol 67, 408–416. Cerca con Google

Lash LH, Jones DP (1993). Mitochondrial Dysfuntion. Meth in Toxicol. Academic Press, Vol. I: San Diego. Cerca con Google

Leigh D. (1951). Subacute necrotizing encephalomyelopathy in an infant. J Neurol Neurosurg Psychiatr 14, 216–221. Cerca con Google

Leonard JV and Schapira AVH (2000a). Mitochondrial respiratory chain disorders I: mitochondrial DNA defects. Lancet 355, 299–304. Cerca con Google

Leonard JV and Schapira AVH (2000b). Mitochondrial respiratory chain disorders II: neurodegenerative disorders and nuclear gene defects. Lancet 355, 389–94. Cerca con Google

Leschelle X, Goubern M, Andriamihaja M, Hervé M. Blottière HM, Couplan E, Gonzalez-Barroso M, Petit C, Pagniez A, Chaumontet C, Mignotte B, Bouillaud F and Blachier F. Cerca con Google

(2005). Adaptative metabolic response of human colonic epithelial cells to the adverse effects of the luminal compound sulfide. Biochim Biophys Acta 1725, 201–212. Cerca con Google

Lesnefsky EJ, Gudz IT, Moghaddas S, Migita CT, Ikeda-Saito M, Turkaly PJ and Hoppel CL (2001). Aging decreases electron transport complex III activity in heart interfibrillar mitochondria by alteration of the cytochrome c binding site J Mol Cell Cardiol 33, 37–47 Cerca con Google

Lightowlers RN and Chrzanowska-Lightowlers ZM (2008) PPR (pentatricopeptide repeat) proteins in mammals: important aids to mitochondrial gene expression. Biochem J 416, 5-6. Cerca con Google

Lindhurst MJ, Fiermonte G, Song S, Struys E, De LF, Schwartzberg PL, Chen A, Castegna A, Verhoeven N, Mathews CK, Palmieri F and Biesecker LG (2006). Knockout of Slc25a19 Cerca con Google

causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia. Proc Natl Acad Sci U S A 103, 15927–15932. Cerca con Google

Mamer OA, Tjoa SS, Scriver CR, Klassen GA (1976). Demonstration of a new mammalian isoleucine catabolic pathway yielding an R series of metabolites. Biochem J Cerca con Google

160, 417–426. Cerca con Google

Mantagos S, Genel M, Tanaka K (1979). Ethylmalonic-adipic aciduria: in vivo and in vitro studies indicating deficiency of activities of multiple acyl-CoA dehydrogenases. J Clin Invest 64, 1580–1589. Cerca con Google

Marin-Garcia J, Goldenthal MJ, Pierpont EM, Ananthakrishnan R and Perez-Atayde A Is Cerca con Google

age a contributory factor of mitochondrial bioenergetic decline and DNA defects in Cerca con Google

idiopathic dilated cardiomyopathy? (1999). Cardiovasc Pathol 8, 217– 222. Cerca con Google

Marobbio CM, Di Noia MA and Palmieri F (2006). Identification of a mitochondrial Cerca con Google

transporter for pyrimidine nucleotides in Saccharomyces cerevisiae: bacterial Cerca con Google

expression, reconstitution and functional characterization. Biochem J 393, 441–446. Cerca con Google

Minai L, Martinovic J, Chretien D, Dumez F, Razavi F, Munnich A, Rötig A (2008). Cerca con Google

Mitochondrial respiratory chain complex assembly and function during human fetal Cerca con Google

development. Mol Genet Metab. 94, 120-126. Cerca con Google

Mineri R, Rimoldi M, Burlina AB, Koskull S, Perletti C, Heese B, von Döbeln U, Mereghetti Cerca con Google

P, Di Meo I, Invernizzi F, Zeviani M, Uziel G, Tiranti V (2008). Identification of new Cerca con Google

mutations in the ETHE1 gene in a cohort of 14 patients presenting with ethylmalonic Cerca con Google

encephalopathy. J Med Genet 45, 473–478. Cerca con Google

Moore A and Golden A (2009). Hypothesis: Bifunctional Mitochondrial Proteins Have Cerca con Google

Centrosomal Functions. Environmental and Molecular Mutagenesis 50, 637-648. Cerca con Google

Morrow G and Tanguay RM (2008). Mitochondria and ageing in Drosophila. Biotechnol J Cerca con Google

3, 728–739. Cerca con Google

Nakano K, Balint E, Ashcroft M and Vousden KH (2000). A ribonucleotide reductase gene Cerca con Google

is a transcriptional target of p53 and p73. Oncogene 19, 4283–4289. Cerca con Google

Nass MM and Nass S (1963). Intramitochondrial Fibers with DNA characteristics. J Cell Cerca con Google

Biol Bd 19, 593–629. Cerca con Google

Neupert W (1997). Protein import into mitochondria. Annu Rev Biochem 66, 863–917. Cerca con Google

Nijtmans LG, Henderson NS and Holt IJ (2002). Blue native electrophoresis to study Cerca con Google

mitochondrial and other protein complexes. Methods 26, 327–334. Cerca con Google

References Cerca con Google

226 Cerca con Google

Nijtmans LG, Sanz MA, Bucko M, Farhoud MH, Feenstra M, Hakkaart GA, Zeviani M, Cerca con Google

Grivell LA (2001). Shy1p occurs in a high molecular weight complex and is required for Cerca con Google

efficient assembly of cytochrome c oxidase in yeast. FEBS Lett 498, 46–51. Cerca con Google

Nishigaki Y, Marti R, Copeland WC and Hirano M (2003). Site-specific somatic Cerca con Google

mitochondrial DNA point mutations in patients with thymidine phosphorylase Cerca con Google

deficiency. J Clin Invest 111, 1913–1921. Cerca con Google

Nishino I, Spinazzola A and Hirano M (1999). Thymidine phosphorylase gene mutations Cerca con Google

in MNGIE, a human mitochondrial disorder. Science 283, 689–692. Cerca con Google

Nobrega FG, Nobrega MP and Tzagoloff A (1992). BCS1, a novel gene required for the Cerca con Google

expression of functional Rieske iron–sulfur protein in Saccharomyces cerevisiae. EMBO Cerca con Google

J 11, 3821–3829. Cerca con Google

Nowaczyk MJ, Lehotay DC, Platt BA, Fisher L, Tan R, Phillips H, Clarke JT (1998). Cerca con Google

Ethylmalonic and methylsuccinic aciduria in ethylmalonic encephalopathy arise from Cerca con Google

abnormal isoleucine metabolism. Metabolism 47, 836–839. Cerca con Google

Ozand PT, Rashed M, Millington DS, Sakati N, Hazzaa S, Rahbeeni Z, Al Odaib A, Youssef Cerca con Google

N, Mazrou A, Gascon GG, Brismar (1994). Ethylmalonic aciduria: an organic acidemia Cerca con Google

with CNS involvement and vasculopathy. Brain Dev 16, 12–22. Cerca con Google

Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB, Ong SE, Walford GA, Sugiana C, Cerca con Google

Boneh A, Chen WK (2008). A mitochondrial protein compendium elucidates complex I Cerca con Google

disease biology. Cell 134, 112–123. Cerca con Google

Palmieri F (2004). The mitochondrial transporter family (SLC25): physiological and Cerca con Google

pathological implications. Pflueger’s Arch 447, 689–709. Cerca con Google

Palmieri L, Runswick MJ, Fiermonte G, Walker JE and Palmieri F (2000). Yeast Cerca con Google

mitochondrial carriers: bacterial expression, biochemical identification and metabolic Cerca con Google

significance. J Bioenerg Biomembr 32, 67–77. Cerca con Google

Papa S (1996). Mitochondrial oxidative phosphorylation changes in the life span. Cerca con Google

Molecular aspects and physiopathological implications. Biochim Biophys Acta 1276, 87- Cerca con Google

105 Cerca con Google

Parks AL. Cook KR, Belvin M, Dompe NA, Fawcett R, Huppert K, Tan LR, Winter CG, Cerca con Google

Bogart KP, Deal JE (2004). Systematic generation of high-resolution deletion coverage of Cerca con Google

the Drosophila melanogaster genome. Nat Genet 36, 288-292. Cerca con Google

Pebay-Peyroula E, Dahout-Gonzalez C, Kahn R, Trezeguet V, Lauquin GJ and Brandolin G Cerca con Google

(2003). Structure of mitochondrial ADP/ATP carrier in complex with Cerca con Google

carboxyatractyloside. Nature 426, 39–44. Cerca con Google

Pequignot MO, Desguerre I, Dey R, Tartari M, Zeviani M, Agostino A, Benelli C, Fouque F, Cerca con Google

Prip-Buus C, Marchant D, Abitbol M, Marsac C (2001). New splicing-site mutations in the Cerca con Google

SURF1 gene in Leigh syndrome patients. J Biol Chem 276(18), 15326{9. Cerca con Google

Pfaffl MW (2001). A new mathematical model for relative quantification in real-time Cerca con Google

RT-PCR. Nucleic Acids Res 29, e45. Cerca con Google

References Cerca con Google

227 Cerca con Google

Piccin A, Salameh A, Benna C, Sandrelli F, Mazzotta G, Zordan M, Rosato E, Kyriacou CP, Cerca con Google

Costa R (2001). Efficient and heritable functional knock-out of an adult phenotype in Cerca con Google

Drosophila using a GAL4-driven hairpin RNA incorporating a heterologous spacer. Cerca con Google

Nucleic Acids Res E55, 12–29. Cerca con Google

Piskur J, Sandrini MP, Knecht W and Munch-Petersen B (2004). Animal Cerca con Google

deoxyribonucleoside kinases: 'forward' and 'retrograde' evolution of their substrate Cerca con Google

specificity. FEBS Lett 560, 3–6. Cerca con Google

Pontarin G, Ferraro P, Hakansson P, Thelander L, Reichard P and Bianchi V (2007). p53R2- Cerca con Google

dependent ribonucleotide reduction provides deoxyribonucleotides in quiescent human Cerca con Google

fibroblasts in the absence of induced DNA damage. J Biol Chem 282, 16820–16828. Cerca con Google

Pontarin G, Ferraro P, Valentino ML, Hirano M, Reichard P and Bianchi V (2006). Cerca con Google

Mitochondrial DNA depletion and thymidine phosphate pool dynamics in a cellular Cerca con Google

model of mitochondrial neurogastrointestinal encephalomyopathy. J Biol Chem 281, Cerca con Google

22720–22728. Cerca con Google

Pontarin G, Gallinaro L, Ferraro P, Reichard P and Bianchi V (2003). Origins of Cerca con Google

mitochondrial thymidine triphosphate: Dynamic relations to cytosolic pools. Proc Natl Cerca con Google

Acad Sci USA 100, 12159–12164. Cerca con Google

Poyau A, Buchet K, Godinot C (1999). Sequence conservation from human to Cerca con Google

prokaryotes of Surf1, a protein involved in cytochrome c oxidase assembly, deficient in Cerca con Google

Leigh syndrome. FEBS Lett 462(3):416{20. Cerca con Google

Rampazzo C, Fabris S, Franzolin E, Crovatto K, Frangini M and Bianchi V (2007). Cerca con Google

Mitochondrial thymidine kinase and the enzymatic network regulating thymidine Cerca con Google

triphosphate pools in cultured human cells. J Biol Chem 282, 34758–34769. Cerca con Google

Rampazzo C, Ferraro P, Pontarin G, Fabris S, Reichard P and Bianchi V (2004). Cerca con Google

Mitochondrial Deoxyribonucleotides, Pool Sizes, Synthesis, and Regulation. J Biol Chem Cerca con Google

279, 17019–17026. Cerca con Google

Rampazzo C, Gallinaro L, Milanesi E, Frigimelica E, Reichard P and Bianchi V (2000). A Cerca con Google

deoxyribonucleotidase in mitochondria: involvement in regulation of dNTPs pools and Cerca con Google

possible link to genetic disease. Proc. Natl. Acad. Sci. USA 97, 8239–8244. Cerca con Google

Regan C and Fuller MT (1990). Interacting genes that affect microtubule function in Cerca con Google

Drosophila melanogaster: two classes of mutations revert the failure to complement Cerca con Google

between haync2 and mutations in tubulin genes. Genetics 125, 77–90. Cerca con Google

Ridderstrom M, Saccucci F, Hellman U, Bergman T, Principato G, Mannervik B (1996). Cerca con Google

Molecular cloning, heterologous expression, and characterization of human glyoxalase Cerca con Google

II. J Biol Chem 271, 319–323. Cerca con Google

Roberts DB and Standen GN (1998). The elements of Drosophila biology and genetics, pp. Cerca con Google

1–54 in Drosophila: A Practical Approach, edited by D. B. Roberts. IRL Press, Oxford. Cerca con Google

Rosenberg MJ, Agarwala R, Bouffard G, Davis J, Fiermonte G, Hilliard MS, Koch T, Cerca con Google

Kalikin LM, Makalowska I, Morton DH (2002). Mutant deoxynucleotide carrier is Cerca con Google

associated with congenital microencephaly. Nat. Genet. 32, 175–179. Cerca con Google

References Cerca con Google

228 Cerca con Google

Rouslin W (1983). Mitochondrial complexes I, II, III, IV, and V in myocardial ischemia Cerca con Google

and autolysis. Am. J. Physiol 244, H743-H748. Cerca con Google

Rouslin W, Millard RW (1981). Mitochondrial inner membrane enzyme defects in Cerca con Google

porcine myocardial ischemia. Am J Physiol240, H308-H313. Cerca con Google

Rouslin W, Ranganathan S (1983). Impaired function of mitochondrial electron transfer Cerca con Google

complex I in canine myocardial ischemia: loss of flavin mononucleotide. J Mol Cell Cerca con Google

Cardiol 15, 537-542. Cerca con Google

Saada A, Shaag A, Mandel H, Nevo Y, Eriksson S and Elpeleg O (2001). Mutant Cerca con Google

mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat Genet Cerca con Google

29, 342–344. Cerca con Google

Sagona AP, Nezis IP, Pedersen NM. Liestøl K, Poulton J, Rusten TE, Skotheim RI, Raiborg Cerca con Google

C and Stenmark H (2010). PtdIns(3)P controls cytokinesis through KIF13Amediated Cerca con Google

recruitment of FYVE-CENT to the midbody. Nat Cell Biol 12, 362-371. Cerca con Google

Sandrelli F, Campesan M, Rossetto G, Benna C, Zieger E (2001). Molecular dissection of Cerca con Google

the 59 region of no-on-transientA of Drosophila melanogaster reveals cis-regulation by Cerca con Google

adjacent dGpi sequences. Genetics 157, 765–775. Cerca con Google

Sass JO, Ensenauer R, Röschinger W, Reich H, Steuerwald U, Schirrmacher O, Engel K, Cerca con Google

Häberle J, Andresen BS, Mégarbané A, Lehnert W, Zschocke J (2008). 2-Methylbutyrylcoenzyme Cerca con Google

A dehydrogenase deficiency: functional and molecular studies on a defect in Cerca con Google

isoleucine catabolism. Mol Genet Metab 93, 30–35. Cerca con Google

Schägger H and von Jagow G (1987). Tricine-sodium dodecyl sulfate-polyacrylamide gel Cerca con Google

electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal Cerca con Google

Biochem 166, 368–379. Cerca con Google

Schägger H, Link TA, Engel WD and von Jagow G (1986). Isolation of the eleven protein Cerca con Google

subunits of the bc1 complex from beef heart. Methods Enzymol 126, 224–237. Cerca con Google

Schon EA (2000). Mitochondrial genetics and disease. Trends Biochem Sci 5, 555–560. Cerca con Google

Sciacco M and Bonilla E (1996). Cytochemistry and immunocytochemistry of Cerca con Google

mitochondria in tissue sections. Methods Enzymol 264, 509–521. Cerca con Google

Shields DC, Sharp PM, Higgins DG, Wright F (1988)."Silent" sites in Drosophila genes Cerca con Google

are not neutral: evidence of selection among synonymous codons. Mol Biol Evol, 5(6), Cerca con Google

704–716. Cerca con Google

Small ID and Peeters N (2000). The PPR motif a TPR-related motif prevalent in plant Cerca con Google

organellar proteins. Trends Biochem. Sci. 25, 46–47. Cerca con Google

Smeitink J, van den Heuvel L and DiMauro S (2001). The genetics and pathology of Cerca con Google

oxidative phosphorylation. Nat Rev Genet 2, 342–352. Cerca con Google

Smeitink JA (2003). Mitochondrial disorders: clinical presentation and diagnostic Cerca con Google

dilemmas. J Inher Metab Dis 26, 199–207. Cerca con Google

References Cerca con Google

229 Cerca con Google

Solans A, Zambrano A and Barrientos A (2004). Cytochrome c oxidase deficiency: from Cerca con Google

yeast to human. Preclinica, 2, 1–13. Cerca con Google

Spinazzola A and Zeviani M (2005). Disorders of nuclear-mitochondrial intergenomic Cerca con Google

signaling. Gene 354, 162–168. Cerca con Google

Szabo C (2007). Hydrogen sulphide and its therapeutic potential. Nat Re. Drug Discov 6, Cerca con Google

917–935. Cerca con Google

Tanaka H, Arakawa H, Yamaguchi T, Shiraishi K, Fukuda S, Matsui K, Takei Y and Cerca con Google

Nakamura Y (2000). A ribonucleotide reductase gene involved in a p53- dependent cellcycle Cerca con Google

checkpoint for DNA damage. Nature 404, 42–49. Cerca con Google

Tanaka K, Ramsdell HS, Baretz BH, Keefe MB, Kean EA, Johnson B (1976). Identification Cerca con Google

of ethylmalonic acid in urine of two patients with the vomiting sickness of Jamaica. Clin Cerca con Google

Chim Acta 69, 105–112. Cerca con Google

Thibault ST, Singer AM, Miyazaki YW, Milash B, Dompe AN, Singh MC,Buchholz R, Cerca con Google

Demsky M, Fawcett R, Francis-Lang LH, Ryner L (2004). A complementary transposon Cerca con Google

toolkit for Drosophila melanogaster. Nat. Genet. advance online publication, 22 February Cerca con Google

(doi:10.1038/ng1314). Cerca con Google

Till BJ, Colbert T, Tompa R, Enns LC, Codomo CA, Johnson JE, Reynolds SH, Henikoff Cerca con Google

JG, Greene EA, Steine MN, Comai L, Henikoff S (2003). High-throughput TILLING for Cerca con Google

functional genomics. Methods Mol Biol 236, 205–220. Cerca con Google

Tiranti V, Briem E, Ferrari G, Lamantea E, Papaleo E, De Gioia L, Rinaldo P, Dickson P, Cerca con Google

Abu-LibdeH B, Heberle L, Owaidha M, Jack RM,,Christensen E, Zeviani M. (2006). Ethe1 Cerca con Google

mutations are a prevalent cause of Ethylmalonic Encephalopathy. J Med Genet 43, 340– Cerca con Google

346. Cerca con Google

Tiranti V, Galimberti C, Nijtamns L, Bovolenta S, Perini MP and Zeviani M (1999a). Cerca con Google

Characterization of SURF-1 expression and Surf-1p function in normal and disease Cerca con Google

conditions. Hum Mol Genet 8, 2533–2540. Cerca con Google

Tiranti V, Hoertnagel K, Carrozzo R, Galimberti C, Munaro M, Granatiero M, Zelante L, Cerca con Google

Gasparini P, Marzella R, Rocchi M (1998). Mutations of SURF-1 in Leigh disease Cerca con Google

associated with cytochrome c oxidase deficiency. Am J Hum Genet 63, 1609-1621. Cerca con Google

Tiranti V, Viscomi C, Hildebrandt T, Di Meo I, Mineri R, Tiveron C, Levitt MD, Prelle A, Cerca con Google

Fagiolari G, Rimoldi, Zeviani M (2009). Loss of Ethe1, a mitochondrial dioxygenase, Cerca con Google

causes fatal sulfide toxicity in ethylmalonic encephalopathy. Nat Med 15, 200–205. Cerca con Google

Tiranti V, D'Adamo P, Briem E, Ferrari G, Mineri R, Lamantea E, Mandel H, Balestri P, Cerca con Google

Garcia-silva MT, Vollmer B, Rinaldo P, Hahn SH, Leonard J, Rahman S, Dionisi-VicI C, Cerca con Google

Garavaglia B, Gasparini P, Zeviani M (2004). Ethylmalonic encephalopathy is caused by Cerca con Google

mutations in Ethe1, a gene encoding a mitochondrial matrix protein. Am J Hum Genet Cerca con Google

74, 239–252. Cerca con Google

Tiranti VM, Jaksh S, Hofman C, Galimberti K, Hoertnagel C (1999b). Loss-of-function Cerca con Google

mutations of SURF1 are specifically associated with Leigh syndrome with cytochrome c Cerca con Google

oxidase deficiency. Ann Neurol 46, 161–166. Cerca con Google

References Cerca con Google

230 Cerca con Google

Todisco S, Agrimi G, Castegna A and Palmieri F (2006). Identification of the Cerca con Google

mitochondrial NAD-transporter in Saccharomyces cerevisiae. J Biol Chem 281, 1524– Cerca con Google

1531. Cerca con Google

van den Ouweland JM, Lemkes HH, Ruitenbeek W, Sandkuijl LA, de Vijlder MF, Cerca con Google

Struyvenberg PA, van de Kamp JJ, Maassen JA (1992). Mutation in mitochondrial Cerca con Google

tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes Cerca con Google

mellitus and deafness. Nat Genet 1, 368–71. Cerca con Google

Vockley J and Ensenauer R (2006). Isovaleric acidemia: new aspects of genetic and Cerca con Google

phenotypic heterogeneity. J Med Genet 142, 95–103. Cerca con Google

Vozza A, Blanco E, Palmieri L and Palmieri F (2004). Identification of the mitochondrial Cerca con Google

GTP/GDP transporter in Saccharomyces cerevisiae. J Biol Chem 279, 20850–20857. Cerca con Google

Wallace DC (1999b). Mitochondrial diseases in man and mouse. Science, 283, 1482–8. Cerca con Google

Wallace DC, Brown MD, Lott MT. (1999). Mitochondrial DNA variation in human Cerca con Google

evolution and disease. Gene 238, 211–30. Cerca con Google

Wallace DC, Zheng X, Lott MT, Shoffner JM, Hodge JA, Kelley RI, Epstein CM, Hopkins Cerca con Google

LC, (1988). Familial mitochondrial encephalomyopathy (MERRF): genetic, Cerca con Google

pathophysiological, and biochemical characterization of a mitochondrial DNA disease. Cerca con Google

Cell 55, 601–610. Cerca con Google

Wang B, Li N, Sui L, Wu Y, Wang X, Wang Q, Xia D, Wan T and Cao X (2004). Cerca con Google

HuBMSC-MCP, a novel member of mitochondrial carrier superfamily, enhances Cerca con Google

dendritic cell endocytosis. Biochem Biophys Res Commun 314, 292–300. Cerca con Google

Wang L, Munch-Petersen B, Herrstrom-Sjoberg A, Hellman U, Bergman T, Jornvall H and Cerca con Google

Eriksson S (1999). Human thymidine kinase 2: molecular cloning and characterization Cerca con Google

of the enzyme activity with antiviral and cytostatic nucleoside substrates. FEBS Lett. Cerca con Google

443, 170–174. Cerca con Google

Wiedemann, N., Frazier, A.E., and Pfanner, N. (2004). The protein import machinery of Cerca con Google

mitochondria. J Biol Chem 279, 14473–14476. Cerca con Google

Wiesner RJ, Ruegg JC, Morano I (1992). Counting target molecules by exponential Cerca con Google

polymerase chain reaction, copy number of mitochondrial DNA in rat tissues. Biochim Cerca con Google

Biophys Acta 183 (2): 553–559. Cerca con Google

Wimplinger I, Morleo M, Rosenberger G, Iaconis D, Orth U, Meinecke P, Lerer I, Ballabio Cerca con Google

A, Gal A, Franco B, and Kutsche K (2006). Mutations of the Mitochondrial Cerca con Google

Holocytochrome c–Type Synthase in X-Linked Dominant Microphthalmia with Linear Cerca con Google

Skin Defects Syndrome AJHG 79, 878-889. Cerca con Google

Wittig I, Braun HP and Schagger H (2006). Blue native PAGE. Nat Protoc 1, 418–428. Cerca con Google

Wu M, Neilson A, Swift AL, Moran R, Tamagnine J, Parslow D, Armistead S, Lemire K, Cerca con Google

Orrell J, Teich J, Chomicz S and Ferrick DA (2007). Multiparameter metabolic analysis Cerca con Google

reveals a close link between attenuated mitochondrial bioenergetic function and Cerca con Google

References Cerca con Google

231 Cerca con Google

enhanced glycolysis dependency in human tumor cells. Am J Physiol Cell Physiol 292, Cerca con Google

C125–C136. Cerca con Google

Xu F, Ackerley C, Maj MC, Addis JBL, Levandovskiy V, Lee J, MacKay N, Cameron J M Cerca con Google

and Robinson BH (2008). Disruption of a mitochondrial RNA-binding protein gene Cerca con Google

results in decreased cytochrome b expression and a marked reduction in ubiquinol– Cerca con Google

cytochrome c reductase activity in mouse heart mitochondria. Biochem J 416, 15–26. Cerca con Google

Yao J, Shoubridge EA (1999). Expression and functional analysis of SURF1 in Leigh Cerca con Google

syndrome patients with cytochrome c oxidase deficiency. Hum Mol Genet, 8(13), 2541{9. Cerca con Google

Yao KM, and. White K (1994). Neural specificity of elav expression: defining a Cerca con Google

Drosophila promoter for directing expression to the nervous system. J Neurochem 63, Cerca con Google

41–51. Cerca con Google

Yoon HR, Hahn SH, Ahn YM, Jang SH, Shin YJ, Lee EH, Ryu KH, Eun BL, Rinaldo P, Cerca con Google

Yamaguchi S (2001). Therapeutic trial in the first three Asian cases of ethylmalonic Cerca con Google

encephalopathy: response to riboflavin. J Inherit Metab Dis 24, 870–873. Cerca con Google

Young P, Leeds JM, Slabough MB and Mathews C (1994). Ribonucleotide reductase: Cerca con Google

evidence for specific association with HeLa cell mitochondria. Biochem Biophys Res Cerca con Google

Commun 203, 9300–9304. Cerca con Google

Zara V, Palmisano I, Conte L and Trumpower BL (2004). Further insights into the Cerca con Google

assembly of the yeast cytochrome bc1 complex based on analysis of single and double Cerca con Google

deletion mutants lacking supernumerary subunits and cytochrome b. Eur J Biochem Cerca con Google

271, 1209–1218. Cerca con Google

Zeviani M and Di Donato S (2004). Mitochondrial disorders. Brain 127, 2153–2172. Cerca con Google

Zhang JC, Sun L, Nie QH, Huang CX, Jia ZS, Wang JP, Lian JQ, Li XH, Wang PZ, Zhang Y Cerca con Google

(2009). Down-regulation of CXCR4 expression by SDF-KDEL in CD34(+) Cerca con Google

hematopoietic stem cells: an antihuman immunodeficiency virus strategy. J Virol Cerca con Google

Methods 16, 30-37. Cerca con Google

Zhang YQ, Roote J, Brogna S, Davis AW, Barbash DA, Nash D and Ashburner M (1999). Cerca con Google

Stress sensitive B encodes an adenine nucleotide translocase in Drosophila melanogaster. Cerca con Google

Genetics 153, 891-903. Cerca con Google

Zhu C, Johansson M and Karlsson A (2000). Incorporation of nucleoside analogs into Cerca con Google

nuclear or mitochondrial DNA is determined by the intracellular phosphorylation site. Cerca con Google

J Biol Chem 275, 26727–26731. Cerca con Google

Zhu Z, Yao J, Johns T, Fu K, Bie ID, Macmillan C, Cuthbert AP, Newbold RF, Wang J, Cerca con Google

Chevrette M, Brown GK, Brown RM, Shoubridge EA (1998). SURF1, encoding a factor Cerca con Google

involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome. Nat Cerca con Google

Genet, 20(4):337{43. Cerca con Google

Zordan M.A, Massironi M, Ducato MG, Te Kronnie G, Costa R (2005). Drosophila Cerca con Google

CAKI/CMG protein, a homolog of human CASK, is essential for regulation of Cerca con Google

neurotransmitter vesicle release. J Neurophysiol 94, 1074–1083. Cerca con Google

References Cerca con Google

232 Cerca con Google

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