MITRAC7 Acts as a COX1-Specific Chaperone and Reveals a Checkpoint during Cytochrome c Oxidase Assembly.

Cell Reports
Sven DennerleinPeter Rehling

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.

References

Oct 2, 2001·American Journal of Medical Genetics·E A Shoubridge
Nov 11, 2003·The Journal of Biological Chemistry·Siôn L WilliamsJan-Willem Taanman
Jul 2, 2004·Human Molecular Genetics·Scot C LearyEric A Shoubridge
Aug 9, 2005·The Biochemical Journal·Lukas StiburekJiri Zeman
Apr 5, 2007·Nature Protocols·Ilka WittigHermann Schägger
Apr 14, 2007·The Journal of Biological Chemistry·Oleh KhalimonchukDennis R Winge
Jan 25, 2008·The EMBO Journal·Takashi Tatsuta, Thomas Langer
Jun 5, 2008·Biochimica Et Biophysica Acta·Antoni BarrientosFlavia Fontanesi
Jul 2, 2008·Biochimica Et Biophysica Acta·Karina WagnerPeter Rehling
Mar 20, 2009·American Journal of Physiology. Cell Physiology·Lukas StiburekJiri Zeman
Aug 26, 2009·Cell·Agnieszka ChacinskaNikolaus Pfanner
Dec 8, 2009·Biochimica Et Biophysica Acta·Martin Ott, Johannes M Herrmann
Dec 24, 2010·Nature Reviews. Molecular Cell Biology·David U MickPeter Rehling
Oct 1, 2011·Biochimica Et Biophysica Acta·Ileana C SotoAntoni Barrientos
Jan 17, 2012·American Journal of Human Genetics·Woranontee WeraarpachaiEric A Shoubridge
Jan 31, 2013·The Journal of Biological Chemistry·Paula ClementeRafael Garesse
Jan 10, 2014·Human Molecular Genetics·Myriam BourensAntoni Barrientos
Jan 28, 2014·American Journal of Human Genetics·Sze Chern LimDavid R Thorburn
May 21, 2014·The Journal of Cell Biology·Markus HildenbeutelMartin Ott
Aug 5, 2014·Cell Metabolism·B Martin Hällberg, Nils-Göran Larsson
Oct 9, 2014·European Journal of Human Genetics : EJHG·Monika OláhováRobert W Taylor
Feb 11, 2015·Journal of Cell Science·Sven Dennerlein, Peter Rehling

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Citations

Apr 24, 2016·Free Radical Biology & Medicine·Raquel Moreno-Loshuertos, José Antonio Enríquez
Oct 4, 2016·Cell·Ricarda Richter-DennerleinSven Dennerlein
Apr 20, 2018·Acta Pharmacologica Sinica·Emma K Mcilwraith, Denise D Belsham
Jun 3, 2020·International Journal of Molecular Sciences·Jia Xin TangMonika Oláhová
Mar 7, 2020·Biological Chemistry·Leticia Veloso Ribeiro FrancoAlexander Tzagoloff
Feb 6, 2016·Clinical Science·Malgorzata RakPierre Rustin
Jun 9, 2017·Oxidative Medicine and Cellular Longevity·Christopher A SinklerMaik Hüttemann
Jul 22, 2018·Essays in Biochemistry·Alba Signes, Erika Fernandez-Vizarra
Jan 11, 2019·Nature Reviews. Molecular Cell Biology·Nikolaus PfannerNils Wiedemann
Aug 8, 2018·Nucleic Acids Research·Elena LavdovskaiaRicarda Richter-Dennerlein
Jan 2, 2019·The Journal of Cell Biology·Frank RichterPeter Rehling
Jun 13, 2018·International Journal of Molecular Sciences·Martha A Schalla, Andreas Stengel
Oct 4, 2020·International Journal of Molecular Sciences·Shane A Watson, Gavin P McStay
Dec 3, 2020·Nucleic Acids Research·Elena LavdovskaiaRicarda Richter-Dennerlein
Nov 2, 2019·Mitochondrion·Mario H Barros, Gavin P McStay
Nov 16, 2020·Molecular and Cellular Endocrinology·Deborah J Good
Jan 14, 2021·International Journal of Molecular Sciences·Margherita Protasoni, Massimo Zeviani
Nov 12, 2020·International Journal of Molecular Sciences·Maria BillertMarek Skrzypski
Sep 6, 2017·Seminars in Cell & Developmental Biology·Alba Timón-GómezAntoni Barrientos
Sep 16, 2017·Biochemical and Biophysical Research Communications·Philip PrinzAndreas Stengel

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