Details

Autor(en) / Beteiligte

• Marsano, René Massimiliano
• Rötig, Agnes
• Calvo, Sarah
• Fernandez-Vizarra, Erika
• Sarzi, Emmanuelle
• Donnini, Claudia
• Chan, Alicia
• Carrara, Franco
• Strisciuglio, Pietro
• Spinazzola, Antonella
• Viscomi, Carlo
• D'Adamo, Pio
• Parini, Rossella
• DiMauro, Salvatore
• Mootha, Vamsi K
• Ferrero, Iliana
• Tiranti, Valeria
• Weiher, Hans
• Gasparini, Paolo
• Zeviani, Massimo

Titel

MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion

Ist Teil von

• Nature genetics, 2006-05, Vol.38 (5), p.570-575

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2006

Quelle

MEDLINE

Beschreibungen/Notizen

• The mitochondrial (mt) DNA depletion syndromes (MDDS) are genetic disorders characterized by a severe, tissue-specific decrease of mtDNA copy number, leading to organ failure. There are two main clinical presentations: myopathic (OMIM 609560) and hepatocerebral (OMIM 251880). Known mutant genes, including TK2 (ref. 2), SUCLA2 (ref. 3), DGUOK (ref. 4) and POLG, account for only a fraction of MDDS cases. We found a new locus for hepatocerebral MDDS on chromosome 2p21-23 and prioritized the genes on this locus using a new integrative genomics strategy. One of the top-scoring candidates was the human ortholog of the mouse kidney disease gene Mpv17 (ref. 8). We found disease-segregating mutations in three families with hepatocerebral MDDS and demonstrated that, contrary to the alleged peroxisomal localization of the MPV17 gene product, MPV17 is a mitochondrial inner membrane protein, and its absence or malfunction causes oxidative phosphorylation (OXPHOS) failure and mtDNA depletion, not only in affected individuals but also in Mpv17−/− mice.