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In a large proportion of cases the problem can be traced to a complex I (NADH\u2010CoQ oxidoreductase) deficiency (Phenotype MIM #252010). Because the complex consists of 44 subunits, there are many potential targets for pathogenic mutations, both on the nuclear and mitochondrial genomes. Surprisingly, however, almost half of the complex I deficiencies are due to defects in as yet unidentified genes that encode proteins other than the structural proteins of the complex. This review attempts to summarize what we know about the molecular basis of complex I deficiencies: mutations in the known structural genes, and mutations in an increasing number of genes encoding \u201cassembly factors\u201d, that is, proteins required for the biogenesis of a functional complex I that are not found in the final complex I. More such genes must be identified before definitive genetic counselling can be applied in all cases of affected families.<\/jats:p>","DOI":"10.1007\/s10545-014-9768-6","type":"journal-article","created":{"date-parts":[[2014,9,15]],"date-time":"2014-09-15T09:03:00Z","timestamp":1410771780000},"page":"405-415","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Mitochondrial disease associated with complex I (NADH\u2010CoQ oxidoreductase) deficiency"],"prefix":"10.1002","volume":"38","author":[{"given":"Immo E.","family":"Scheffler","sequence":"first","affiliation":[{"name":"Division of Biology (Molecular Biology Section) University of California San Diego 9500 Gilman Dr. La Jolla CA 92093\u20100322 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