The LYR factors sdhaf1 and SDHAF3 mediate maturation of the iron-sulfur subunit of succinate dehydrogenase

Un Na, Wendou Yu, James Cox, Daniel K. Bricker, Knut Brockmann, Jared Rutter, Carl S. Thummel, Dennis R. Winge

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Summary 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.

Original languageEnglish (US)
Pages (from-to)253-266
Number of pages14
JournalCell Metabolism
Volume20
Issue number2
DOIs
StatePublished - Aug 5 2014

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Na, U., Yu, W., Cox, J., Bricker, D. K., Brockmann, K., Rutter, J., Thummel, C. S., & Winge, D. R. (2014). The LYR factors sdhaf1 and SDHAF3 mediate maturation of the iron-sulfur subunit of succinate dehydrogenase. Cell Metabolism, 20(2), 253-266. https://doi.org/10.1016/j.cmet.2014.05.014