Mitochondrial biogenesis and functions depend on the import of precursor proteins via the 'translocase of the outer membrane' (TOM complex). Defects in protein import lead to an accumulation of mitochondrial precursor proteins that induces a range of cellular stress responses. However, constitutive quality-control mechanisms that clear trapped precursor proteins from the TOM channel under non-stress conditions have remained unknown. Here we report that in Saccharomyces cerevisiae Ubx2, which functions in endoplasmic reticulum-associated degradation, is crucial for this quality-control process. A pool of Ubx2 binds to the TOM complex to recruit the AAA ATPase Cdc48 for removal of arrested precursor proteins from the TOM channel. This mitochondrial protein translocation-associated degradation (mitoTAD) pathway continuously monitors the TOM complex under non-stress conditions to prevent clogging of the TOM channel with precursor proteins. The mitoTAD pathway ensures that mitochondria maintain their full protein-import capacity, and protects cells against proteotoxic stress induced by impaired transport of proteins into mitochondria.
%0 Journal Article
%1 martenssonMitochondrialProteinTranslocationassociated2019a
%A M\aartensson, Christoph U.
%A Priesnitz, Chantal
%A Song, Jiyao
%A Ellenrieder, Lars
%A Doan, Kim Nguyen
%A Boos, Felix
%A Floerchinger, Alessia
%A Zufall, Nicole
%A Oeljeklaus, Silke
%A Warscheid, Bettina
%A Becker, Thomas
%C England
%D 2019
%J Nature
%K *Proteolysis,Carrier Complex Containing Degradation,Membrane Import Membrane Precursor Protein Protein/metabolism Proteins,Mitochondrial Proteins/*metabolism,Protein Proteins/metabolism,Endoplasmic Proteins/metabolism,Mitochondria/*metabolism,Mitochondrial Proteins/metabolism,Mitochondrial Proteins/metabolism,Saccharomyces Reticulum-Associated Transport Transport,Saccharomyces cerevisiae cerevisiae/*cytology/*metabolism,to_read,Valosin
%N 7758
%P 679--683
%R 10.1038/s41586-019-1227-y
%T Mitochondrial Protein Translocation-Associated Degradation.
%V 569
%X Mitochondrial biogenesis and functions depend on the import of precursor proteins via the 'translocase of the outer membrane' (TOM complex). Defects in protein import lead to an accumulation of mitochondrial precursor proteins that induces a range of cellular stress responses. However, constitutive quality-control mechanisms that clear trapped precursor proteins from the TOM channel under non-stress conditions have remained unknown. Here we report that in Saccharomyces cerevisiae Ubx2, which functions in endoplasmic reticulum-associated degradation, is crucial for this quality-control process. A pool of Ubx2 binds to the TOM complex to recruit the AAA ATPase Cdc48 for removal of arrested precursor proteins from the TOM channel. This mitochondrial protein translocation-associated degradation (mitoTAD) pathway continuously monitors the TOM complex under non-stress conditions to prevent clogging of the TOM channel with precursor proteins. The mitoTAD pathway ensures that mitochondria maintain their full protein-import capacity, and protects cells against proteotoxic stress induced by impaired transport of proteins into mitochondria.
@article{martenssonMitochondrialProteinTranslocationassociated2019a,
abstract = {Mitochondrial biogenesis and functions depend on the import of precursor proteins via the 'translocase of the outer membrane' (TOM complex). Defects in protein import lead to an accumulation of mitochondrial precursor proteins that induces a range of cellular stress responses. However, constitutive quality-control mechanisms that clear trapped precursor proteins from the TOM channel under non-stress conditions have remained unknown. Here we report that in Saccharomyces cerevisiae Ubx2, which functions in endoplasmic reticulum-associated degradation, is crucial for this quality-control process. A pool of Ubx2 binds to the TOM complex to recruit the AAA ATPase Cdc48 for removal of arrested precursor proteins from the TOM channel. This mitochondrial protein translocation-associated degradation (mitoTAD) pathway continuously monitors the TOM complex under non-stress conditions to prevent clogging of the TOM channel with precursor proteins. The mitoTAD pathway ensures that mitochondria maintain their full protein-import capacity, and protects cells against proteotoxic stress induced by impaired transport of proteins into mitochondria.},
added-at = {2024-05-17T13:01:35.000+0200},
address = {England},
author = {M{\aa}rtensson, Christoph U. and Priesnitz, Chantal and Song, Jiyao and Ellenrieder, Lars and Doan, Kim Nguyen and Boos, Felix and Floerchinger, Alessia and Zufall, Nicole and Oeljeklaus, Silke and Warscheid, Bettina and Becker, Thomas},
biburl = {https://www.bibsonomy.org/bibtex/2816aab368fd8723c529e49d00a14308d/warscheidlab},
doi = {10.1038/s41586-019-1227-y},
interhash = {731404758d0e480ead4a023851331d9e},
intrahash = {816aab368fd8723c529e49d00a14308d},
issn = {1476-4687 0028-0836},
journal = {Nature},
keywords = {*Proteolysis,Carrier Complex Containing Degradation,Membrane Import Membrane Precursor Protein Protein/metabolism Proteins,Mitochondrial Proteins/*metabolism,Protein Proteins/metabolism,Endoplasmic Proteins/metabolism,Mitochondria/*metabolism,Mitochondrial Proteins/metabolism,Mitochondrial Proteins/metabolism,Saccharomyces Reticulum-Associated Transport Transport,Saccharomyces cerevisiae cerevisiae/*cytology/*metabolism,to_read,Valosin},
langid = {english},
month = may,
number = 7758,
pages = {679--683},
pmid = {31118508},
timestamp = {2024-05-17T13:01:35.000+0200},
title = {Mitochondrial Protein Translocation-Associated Degradation.},
volume = 569,
year = 2019
}