Mining yeast in silico unearths a golden nugget for mitochondrial biology.
NADH:ubiquinone oxidoreductase (complex I) of the electron transport chain is a multimeric mitochondrial enzyme of approximately 1000 kDa consisting of 46 different proteins encoded by both the mitochondrial and nuclear genomes. Little is known about the cellular mechanisms and protein chaperones that guide its assembly. In this issue of the JCI, Ogilvie et al. use genomic sequence data to compare the proteins produced by yeasts with and without complex I in order to generate a list of proteins whose human orthologs might serve as complex I assembly proteins. The gene encoding one of these candidate proteins, B17.2L, was found to harbor a nonsense mutation in one of 28 patients with a deficiency of complex I. B17.2L associated with subcomplexes that are seen when complex I assembly is incomplete. The research described here combines clever model organism genomics and bioinformatics with sophisticated human molecular and biochemical genetics to identify the first mammalian protein required for the normal assembly of complex I.
Nussbaum
Robert L
RL
Genetic Diseases Research Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA. rlnuss@mail.nih.gov
D000818:Animals; D018389:Codon, Nonsense / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D004579:Electron Transport / Q000235:genetics; D042967:Electron Transport Complex I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016681:Genome, Fungal / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D010085:Oxidative Phosphorylation; D015003:Yeasts / Q000201:enzymology* / Q000235:genetics
D018389:Codon, Nonsense; D018832:Molecular Chaperones; D042967:Electron Transport Complex I