Mitochondrial respiratory-chain complexes assemble from subunits of dual genetic origin assisted by specialized assembly factors. Whereas core subunits are translated on mitochondrial ribosomes, others are imported after cytosolic translation. How imported subunits are ushered to assembly intermediates containing mitochondria-encoded subunits is unresolved. Here, we report a comprehensive dissection of early cytochrome c oxidase assembly intermediates containing proteins required for normal mitochondrial translation and reveal assembly factors promoting biogenesis of human respiratory-chain complexes. We find that TIM21, a subunit of the inner-membrane presequence translocase, is also present in the major assembly intermediates containing newly mitochondria-synthesized and imported respiratory-chain subunits, which we term MITRAC complexes. Human TIM21 is dispensable for protein import but required for integration of early-assembling, presequence-containing subunits into respiratory-chain intermediates. We establish an unexpected molecular link between the TIM23 transport machinery and assembly of respiratory-chain complexes that regulate mitochondrial protein synthesis in response to their assembly state.
%0 Journal Article
%1 mickMITRACLinksMitochondrial2012a
%A Mick, David U.
%A Dennerlein, Sven
%A Wiese, Heike
%A Reinhold, Robert
%A Pacheu-Grau, David
%A Lorenzi, Isotta
%A Sasarman, Florin
%A Weraarpachai, Woranontee
%A Shoubridge, Eric A.
%A Warscheid, Bettina
%A Rehling, Peter
%C United States
%D 2012
%J Cell
%K 1/genetics/metabolism,Cytosol/metabolism,Electron Biosynthesis,to_read Complex Cyclooxygenase IV/*metabolism,Humans,Membrane Import Membrane Precursor Protein Proteins,Mitochondrial Proteins/*metabolism,Mitochondrial Proteins/chemistry/*metabolism,Membrane Proteins/chemistry/*metabolism,Mitochondria/chemistry/genetics/*metabolism,Mitochondrial Proteins/chemistry/*metabolism,Protein Transport
%N 7
%P 1528--1541
%R 10.1016/j.cell.2012.11.053
%T MITRAC Links Mitochondrial Protein Translocation to Respiratory-Chain Assembly and Translational Regulation.
%V 151
%X Mitochondrial respiratory-chain complexes assemble from subunits of dual genetic origin assisted by specialized assembly factors. Whereas core subunits are translated on mitochondrial ribosomes, others are imported after cytosolic translation. How imported subunits are ushered to assembly intermediates containing mitochondria-encoded subunits is unresolved. Here, we report a comprehensive dissection of early cytochrome c oxidase assembly intermediates containing proteins required for normal mitochondrial translation and reveal assembly factors promoting biogenesis of human respiratory-chain complexes. We find that TIM21, a subunit of the inner-membrane presequence translocase, is also present in the major assembly intermediates containing newly mitochondria-synthesized and imported respiratory-chain subunits, which we term MITRAC complexes. Human TIM21 is dispensable for protein import but required for integration of early-assembling, presequence-containing subunits into respiratory-chain intermediates. We establish an unexpected molecular link between the TIM23 transport machinery and assembly of respiratory-chain complexes that regulate mitochondrial protein synthesis in response to their assembly state.
@article{mickMITRACLinksMitochondrial2012a,
abstract = {Mitochondrial respiratory-chain complexes assemble from subunits of dual genetic origin assisted by specialized assembly factors. Whereas core subunits are translated on mitochondrial ribosomes, others are imported after cytosolic translation. How imported subunits are ushered to assembly intermediates containing mitochondria-encoded subunits is unresolved. Here, we report a comprehensive dissection of early cytochrome c oxidase assembly intermediates containing proteins required for normal mitochondrial translation and reveal assembly factors promoting biogenesis of human respiratory-chain complexes. We find that TIM21, a subunit of the inner-membrane presequence translocase, is also present in the major assembly intermediates containing newly mitochondria-synthesized and imported respiratory-chain subunits, which we term MITRAC complexes. Human TIM21 is dispensable for protein import but required for integration of early-assembling, presequence-containing subunits into respiratory-chain intermediates. We establish an unexpected molecular link between the TIM23 transport machinery and assembly of respiratory-chain complexes that regulate mitochondrial protein synthesis in response to their assembly state.},
added-at = {2024-05-17T13:01:35.000+0200},
address = {United States},
author = {Mick, David U. and Dennerlein, Sven and Wiese, Heike and Reinhold, Robert and {Pacheu-Grau}, David and Lorenzi, Isotta and Sasarman, Florin and Weraarpachai, Woranontee and Shoubridge, Eric A. and Warscheid, Bettina and Rehling, Peter},
biburl = {https://www.bibsonomy.org/bibtex/220f383ed17f06d8c438584f465fd7991/warscheidlab},
copyright = {Copyright {\copyright} 2012 Elsevier Inc. All rights reserved.},
doi = {10.1016/j.cell.2012.11.053},
interhash = {9cddb8041603fd71128ddbc32bed3811},
intrahash = {20f383ed17f06d8c438584f465fd7991},
issn = {1097-4172 0092-8674},
journal = {Cell},
keywords = {1/genetics/metabolism,Cytosol/metabolism,Electron Biosynthesis,to_read Complex Cyclooxygenase IV/*metabolism,Humans,Membrane Import Membrane Precursor Protein Proteins,Mitochondrial Proteins/*metabolism,Mitochondrial Proteins/chemistry/*metabolism,Membrane Proteins/chemistry/*metabolism,Mitochondria/chemistry/genetics/*metabolism,Mitochondrial Proteins/chemistry/*metabolism,Protein Transport},
langid = {english},
month = dec,
number = 7,
pages = {1528--1541},
pmid = {23260140},
timestamp = {2024-05-17T13:01:35.000+0200},
title = {{{MITRAC}} Links Mitochondrial Protein Translocation to Respiratory-Chain Assembly and Translational Regulation.},
volume = 151,
year = 2012
}