MITRAC7 Acts as a COX1-Specific Chaperone and Reveals a Checkpoint during Cytochrome c Oxidase Assembly
Sven Dennerlein,
Silke Oeljeklaus,
Daniel Jans,
Christin Hellwig,
Bettina Bareth,
Stefan Jakobs,
Markus Deckers,
Bettina Warscheid,
Peter Rehling
Affiliations
Sven Dennerlein
Department of Cellular Biochemistry, University of Göttingen, 37073 Göttingen, Germany
Silke Oeljeklaus
Department of Biochemistry and Functional Proteomics, Faculty of Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany
Daniel Jans
Department of NanoBiophotonics, Mitochondrial Structure and Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany
Christin Hellwig
Department of Cellular Biochemistry, University of Göttingen, 37073 Göttingen, Germany
Bettina Bareth
Department of Cellular Biochemistry, University of Göttingen, 37073 Göttingen, Germany
Stefan Jakobs
Department of NanoBiophotonics, Mitochondrial Structure and Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany
Markus Deckers
Department of Cellular Biochemistry, University of Göttingen, 37073 Göttingen, Germany
Bettina Warscheid
Department of Biochemistry and Functional Proteomics, Faculty of Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany
Peter Rehling
Department of Cellular Biochemistry, University of Göttingen, 37073 Göttingen, Germany
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.
