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

• Published in: Biochimica et biophysica acta 2016-12, Vol.1857 (12), p.1935-1942
• Main Authors: D'Imprima, Edoardo, Mills, Deryck J., Parey, Kristian, Brandt, Ulrich, Kühlbrandt, Werner, Zickermann, Volker, Vonck, Janet
• Format: Article
• Language: English
• Subjects: Catalysis; Complex I; Cryo-electron microscopy; Cryoelectron Microscopy; Cysteine - analogs & derivatives; Cysteine - metabolism; Electron transport chain; 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; Mitochondria - enzymology; Mitochondria - ultrastructure; Models, Molecular; NADH:ubiquinone oxidoreductase; 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
• ISSN: 0005-2728; 0006-3002; 1879-2650
• DOI: 10.1016/j.bbabio.2016.09.014

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. [Display omitted] •A 7.9Å cryo-EM map of Yarrowia lipolytica complex I shows all subunits•20% of the particles show an extra density at the base of the matrix arm•The density was identified as the transiently attached sulfur transferase ST1•The complex I preparation has high ST1 activity