The LYR factors SDHAF1 and SDHAF3 mediate maturation of the iron-sulfur subunit of succinate dehydrogenase

Cell Metab. 2014 Aug 5;20(2):253-66. doi: 10.1016/j.cmet.2014.05.014. Epub 2014 Jun 19.


Disorders arising from impaired assembly of succinate dehydrogenase (SDH) result in a myriad of pathologies, consistent with its unique role in linking the citric acid cycle and electron transport chain. In spite of this critical function, however, only a few factors are known to be required for SDH assembly and function. We show here that two factors, Sdh6 (SDHAF1) and Sdh7 (SDHAF3), mediate maturation of the FeS cluster SDH subunit (Sdh2/SDHB). Yeast and Drosophila lacking SDHAF3 are impaired in SDH activity with reduced levels of Sdh2. Drosophila lacking the Sdh7 ortholog SDHAF3 are hypersensitive to oxidative stress and exhibit muscular and neuronal dysfunction. Yeast studies revealed that Sdh6 and Sdh7 act together to promote Sdh2 maturation by binding to a Sdh1/Sdh2 intermediate, protecting it from the deleterious effects of oxidants. These studies in yeast and Drosophila raise the possibility that SDHAF3 mutations may be associated with idiopathic SDH-associated diseases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • HEK293 Cells
  • Humans
  • Iron / chemistry
  • Mutation
  • Oxidative Stress / drug effects
  • Paraquat / toxicity
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Proteins / antagonists & inhibitors
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Reactive Oxygen Species / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Succinate Dehydrogenase / chemistry
  • Succinate Dehydrogenase / genetics
  • Succinate Dehydrogenase / metabolism*
  • Sulfur / chemistry


  • Drosophila Proteins
  • Protein Subunits
  • Proteins
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • SDH2 protein, S cerevisiae
  • SDHAF1 protein, human
  • Saccharomyces cerevisiae Proteins
  • Sulfur
  • Iron
  • Succinate Dehydrogenase
  • Paraquat