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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


  • Hao HX
  • Khalimonchuk O
  • Schraders M
  • Dephoure N
  • Bayley JP
  • Kunst H
  • Devilee P
  • Cremers CW
  • Schiffman JD
  • Bentz BG
  • Gygi SP
  • Winge DR
  • Kremer H
  • Rutter J


Science (New York, N.Y.)

Publication Data

August 28, 2009

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK071962
  • Agency: NIGMS NIH HHS, Id: GM087346
  • Agency: NIEHS NIH HHS, Id: R01 ES003817

Mesh Terms

  • 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