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Spinazzola A, et al.  (2006) MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion. Nat Genet 38(5):570-5

Abstract: 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, SUCLA2, DGUOK 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. 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.

Status: Published

Type: Journal Article | Research Support, Non-U.S. Gov't

PubMed ID: 16582910

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Spinazzola A Viscomi C Fernandez-Vizarra E Carrara F D'Adamo P Calvo S Marsano RM Donnini C Weiher H Strisciuglio P Parini R Sarzi E Chan A DiMauro S Rotig A Gasparini P Ferrero I Mootha VK Tiranti V Zeviani M Papers in SGD Colleagues in SGD PubMed Google Scholar

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