title: MITRAC7 Acts as a COX1-Specific Chaperone and Reveals a Checkpoint during Cytochrome c Oxidase Assembly.
abstract: Cytochrome c oxidase, the terminal enzyme of the respiratory chain, is assembled from mitochondria- and nuclear-encoded subunits. The MITRAC complex represents the central assembly intermediate during this process as it receives imported subunits and regulates mitochondrial translation of COX1 mRNA. The molecular processes that promote and regulate the progression of assembly downstream of MITRAC are still unknown. Here, we identify MITRAC7 as a constituent of a late form of MITRAC and as a COX1-specific chaperone. MITRAC7 is required for cytochrome c oxidase biogenesis. Surprisingly, loss of MITRAC7 or an increase in its amount causes selective cytochrome c oxidase deficiency in human cells. We demonstrate that increased MITRAC7 levels stabilize and trap COX1 in MITRAC, blocking progression in the assembly process. In contrast, MITRAC7 deficiency leads to turnover of newly synthesized COX1. Accordingly, MITRAC7 affects the biogenesis pathway by stabilizing newly synthesized COX1 in assembly intermediates, concomitantly preventing turnover.
authors: Department of Cellular Biochemistry, University of Göttingen, 37073 Göttingen, Germany.
authors: Sven
authors: S
authors: Dennerlein
authors: Department of Biochemistry and Functional Proteomics, Faculty of Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
authors: Silke
authors: S
authors: Oeljeklaus
authors: Department of NanoBiophotonics, Mitochondrial Structure and Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
authors: Daniel
authors: D
authors: Jans
authors: Department of Cellular Biochemistry, University of Göttingen, 37073 Göttingen, Germany.
authors: Christin
authors: C
authors: Hellwig
authors: Department of Cellular Biochemistry, University of Göttingen, 37073 Göttingen, Germany.
authors: Bettina
authors: B
authors: Bareth
authors: Department of NanoBiophotonics, Mitochondrial Structure and Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; Department of Neurology, University of Göttingen, 37073 Göttingen, Germany.
authors: Stefan
authors: S
authors: Jakobs
authors: Department of Cellular Biochemistry, University of Göttingen, 37073 Göttingen, Germany.
authors: Markus
authors: M
authors: Deckers
authors: Department of Biochemistry and Functional Proteomics, Faculty of Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
authors: Bettina
authors: B
authors: Warscheid
authors: Department of Cellular Biochemistry, University of Göttingen, 37073 Göttingen, Germany; Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany. Electronic address: peter.rehling@medizin.uni-goettingen.de.
authors: Peter
authors: P
authors: Rehling
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D003576:Electron Transport Complex IV / Q000378:metabolism*; D004795:Enzyme Stability; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism / Q000502:physiology*; D018832:Molecular Chaperones / Q000502:physiology*; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport
chemical_list: C578539:COA3 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D021122:Protein Subunits; C000608523:SMIM20 protein, human; D003576:Electron Transport Complex IV