Cryo-EM structure of respiratory complex I reveals a link to mitochondrial sulfur metabolism.
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.
Max Planck Institute of Biophysics, Department of Structural Biology, Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany.
Edoardo
E
D'Imprima
Max Planck Institute of Biophysics, Department of Structural Biology, Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany.
Deryck J
DJ
Mills
Max Planck Institute of Biophysics, Department of Structural Biology, Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany.
Kristian
K
Parey
Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands; Cluster of Excellence Frankfurt "Macromolecular Complexes," Goethe University, 60438 Frankfurt am Main, Germany.
Ulrich
U
Brandt
Max Planck Institute of Biophysics, Department of Structural Biology, Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany.
Werner
W
Kühlbrandt
Cluster of Excellence Frankfurt "Macromolecular Complexes," Goethe University, 60438 Frankfurt am Main, Germany; Structural Bioenergetics Group, Institute of Biochemistry II, Medical School, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany. Electronic address: zickermann@med.uni-frankfurt.de.
Volker
V
Zickermann
Max Planck Institute of Biophysics, Department of Structural Biology, Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany. Electronic address: janet.vonck@biophys.mpg.de.
Janet
J
Vonck
D002384:Catalysis; D020285:Cryoelectron Microscopy; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D042967:Electron Transport Complex I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D004734:Energy Metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D006862:Hydrogen Sulfide / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology* / Q000648:ultrastructure; D008958:Models, Molecular; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000378:metabolism*; D019885:Sulfur Group Transferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D025062:Yarrowia / Q000201:enzymology* / Q000235:genetics / Q000648:ultrastructure
D005656:Fungal Proteins; C008366:3-mercaptopyruvic acid; D013455:Sulfur; D019885:Sulfur Group Transferases; D042967:Electron Transport Complex I; D003545:Cysteine; D006862:Hydrogen Sulfide
Complex I; Cryo-electron microscopy; Electron transport chain; Mitochondria; NADH:ubiquinone oxidoreductase; Sulfur metabolism