SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma.
Mammalian mitochondria contain about 1100 proteins, nearly 300 of which are uncharacterized. Given the well-established role of mitochondrial defects in human disease, functional characterization of these proteins may shed new light on disease mechanisms. Starting with yeast as a model system, we investigated an uncharacterized but highly conserved mitochondrial protein (named here Sdh5). Both yeast and human Sdh5 interact with the catalytic subunit of the succinate dehydrogenase (SDH) complex, a component of both the electron transport chain and the tricarboxylic acid cycle. Sdh5 is required for SDH-dependent respiration and for Sdh1 flavination (incorporation of the flavin adenine dinucleotide cofactor). Germline loss-of-function mutations in the human SDH5 gene, located on chromosome 11q13.1, segregate with disease in a family with hereditary paraganglioma, a neuroendocrine tumor previously linked to mutations in genes encoding SDH subunits. Thus, a mitochondrial proteomics analysis in yeast has led to the discovery of a human tumor susceptibility gene.
Pubmed ID: 19628817 RIS Download
Amino Acid Sequence | Cell Line | Cell Line, Tumor | Female | Flavin-Adenine Dinucleotide | Flavoproteins | Germ-Line Mutation | Haplotypes | Humans | Inheritance Patterns | Male | Mitochondria | Mitochondrial Proteins | Molecular Sequence Data | Oxygen Consumption | Paraganglioma | Pedigree | Protein Subunits | Proteomics | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins | Succinate Dehydrogenase