SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma Academic Article uri icon

Overview

MeSH Major

  • Germ-Line Mutation
  • Mitochondria
  • Mitochondrial Proteins
  • Paraganglioma
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Succinate Dehydrogenase

abstract

  • 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.

publication date

  • September 7, 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3881419

Digital Object Identifier (DOI)

  • 10.1126/science.1175689

PubMed ID

  • 19628817

Additional Document Info

start page

  • 1139

end page

  • 42

volume

  • 325

number

  • 5944