Emerging concepts in the flavinylation of succinate dehydrogenase

Biochim Biophys Acta. 2013 May;1827(5):627-36. doi: 10.1016/j.bbabio.2013.01.012. Epub 2013 Feb 1.

Abstract

The Succinate Dehydrogenase (SDH) heterotetrameric complex catalyzes the oxidation of succinate to fumarate in the tricarboxylic acid (TCA) cycle and in the aerobic respiratory chains of eukaryotes and bacteria. Essential in this catalysis is the covalently-linked cofactor flavin adenine dinucleotide (FAD) in subunit1 (Sdh1) of the SDH enzyme complex. The mechanism of FAD insertion and covalent attachment to Sdh1 is unknown. Our working concept of this flavinylation process has relied mostly on foundational works from the 1990s and by applying the principles learned from other enzymes containing a similarly linked FAD. The discovery of the flavinylation factor Sdh5, however, has provided new insight into the possible mechanism associated with Sdh1 flavinylation. This review focuses on encapsulating prior and recent advances towards understanding the mechanism associated with flavinylation of Sdh1 and how this flavinylation process affects the overall assembly of SDH. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease.

Publication types

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

MeSH terms

  • Electron Transport Complex II / chemistry
  • Electron Transport Complex II / metabolism*
  • Flavin-Adenine Dinucleotide / metabolism*
  • Humans
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / metabolism*
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Succinate Dehydrogenase / chemistry
  • Succinate Dehydrogenase / metabolism*

Substances

  • Mitochondrial Proteins
  • SDH1 protein, S cerevisiae
  • SDH5 protein, S cerevisiae
  • SDHAF2 protein, human
  • Saccharomyces cerevisiae Proteins
  • Flavin-Adenine Dinucleotide
  • Electron Transport Complex II
  • SDHA protein, human
  • Succinate Dehydrogenase