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

  • 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.

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Metadaten
Document Type:Article
Language:English
Parent Title (English):Nature Genetics
Volume:38
Issue:5
First Page:570
Last Page:575
ISSN:1061-4036
DOI:https://doi.org/10.1038/ng1765
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=16582910
Publisher:Nature Publishing Group
Date of first publication:2006/04/02
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Institut für funktionale Gen-Analytik (IfGA)
Dewey Decimal Classification (DDC):500 Naturwissenschaften und Mathematik / 570 Biowissenschaften; Biologie / 576 Genetik und Evolution
Entry in this database:2015/04/02