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.
%0 Journal Article
%1 dennerleinMITRAC7ActsCOX1Specific2015
%A Dennerlein, Sven
%A Oeljeklaus, Silke
%A Jans, Daniel
%A Hellwig, Christin
%A Bareth, Bettina
%A Jakobs, Stefan
%A Deckers, Markus
%A Warscheid, Bettina
%A Rehling, Peter
%C United States
%D 2015
%J Cell reports
%K Acid Amino Cells,Humans,Membrane Chaperones/*physiology,Molecular Complex Data,Protein IV/*metabolism,Enzyme Line Membranes/metabolism,Mitochondrial Multimerization,Protein Proteins/metabolism/*physiology,Mitochondrial Proteins/metabolism/*physiology,Molecular Sequence Sequence,Cell Stability,HEK293 Subunits/metabolism,Protein Transport Transport,to_read Tumor,Electron
%N 10
%P 1644--1655
%R 10.1016/j.celrep.2015.08.009
%T MITRAC7 Acts as a COX1-Specific Chaperone and Reveals a Checkpoint during Cytochrome c Oxidase Assembly.
%V 12
%X 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.
@article{dennerleinMITRAC7ActsCOX1Specific2015,
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.},
added-at = {2024-05-17T13:01:35.000+0200},
address = {United States},
author = {Dennerlein, Sven and Oeljeklaus, Silke and Jans, Daniel and Hellwig, Christin and Bareth, Bettina and Jakobs, Stefan and Deckers, Markus and Warscheid, Bettina and Rehling, Peter},
biburl = {https://www.bibsonomy.org/bibtex/29988401b1fc0a269887d6df63355df04/warscheidlab},
copyright = {Copyright {\copyright} 2015 The Authors. Published by Elsevier Inc. All rights reserved.},
doi = {10.1016/j.celrep.2015.08.009},
interhash = {486db81659e121b9446de7fff5be9c5e},
intrahash = {9988401b1fc0a269887d6df63355df04},
issn = {2211-1247},
journal = {Cell reports},
keywords = {Acid Amino Cells,Humans,Membrane Chaperones/*physiology,Molecular Complex Data,Protein IV/*metabolism,Enzyme Line Membranes/metabolism,Mitochondrial Multimerization,Protein Proteins/metabolism/*physiology,Mitochondrial Proteins/metabolism/*physiology,Molecular Sequence Sequence,Cell Stability,HEK293 Subunits/metabolism,Protein Transport Transport,to_read Tumor,Electron},
langid = {english},
month = sep,
number = 10,
pages = {1644--1655},
pmid = {26321642},
timestamp = {2024-05-17T13:01:35.000+0200},
title = {{{MITRAC7 Acts}} as a {{COX1-Specific Chaperone}} and {{Reveals}} a {{Checkpoint}} during {{Cytochrome}} c {{Oxidase Assembly}}.},
volume = 12,
year = 2015
}