Cryo-EM structure of respiratory complex I reveals a link to mitochondrial sulfur metabolism

Biochim Biophys Acta. 2016 Dec;1857(12):1935-1942. doi: 10.1016/j.bbabio.2016.09.014. Epub 2016 Sep 30.

Abstract

Mitochondrial complex I is a 1MDa membrane protein complex with a central role in aerobic energy metabolism. The bioenergetic core functions are executed by 14 central subunits that are conserved from bacteria to man. Despite recent progress in structure determination, our understanding of the function of the ~30 accessory subunits associated with the mitochondrial complex is still limited. We have investigated the structure of complex I from the aerobic yeast Yarrowia lipolytica by cryo-electron microscopy. Our density map at 7.9Å resolution closely matches the 3.6-3.9Å X-ray structure of the Yarrowia lipolytica complex. However, the cryo-EM map indicated an additional subunit on the side of the matrix arm above the membrane surface, pointing away from the membrane arm. The density, which is not present in any previously described complex I structure and occurs in about 20 % of the particles, was identified as the accessory sulfur transferase subunit ST1. The Yarrowia lipolytica complex I preparation is active in generating H2S from the cysteine derivative 3-mercaptopyruvate, catalyzed by ST1. We thus provide evidence for a link between respiratory complex I and mitochondrial sulfur metabolism.

Keywords: Complex I; Cryo-electron microscopy; Electron transport chain; Mitochondria; NADH:ubiquinone oxidoreductase; Sulfur metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Cryoelectron Microscopy*
  • Cysteine / analogs & derivatives
  • Cysteine / metabolism
  • Electron Transport Complex I / chemistry
  • Electron Transport Complex I / genetics
  • Electron Transport Complex I / metabolism*
  • Electron Transport Complex I / ultrastructure
  • Energy Metabolism*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Fungal Proteins / ultrastructure
  • Hydrogen Sulfide / metabolism
  • Mitochondria / enzymology*
  • Mitochondria / ultrastructure
  • Models, Molecular
  • Protein Conformation
  • Structure-Activity Relationship
  • Sulfur / metabolism*
  • Sulfur Group Transferases / chemistry
  • Sulfur Group Transferases / genetics
  • Sulfur Group Transferases / metabolism*
  • Sulfur Group Transferases / ultrastructure
  • Yarrowia / enzymology*
  • Yarrowia / genetics
  • Yarrowia / ultrastructure

Substances

  • Fungal Proteins
  • 3-mercaptopyruvic acid
  • Sulfur
  • Sulfur Group Transferases
  • Electron Transport Complex I
  • Cysteine
  • Hydrogen Sulfide