RRC ID 46609
Author Heo JM, Livnat-Levanon N, Taylor EB, Jones KT, Dephoure N, Ring J, Xie J, Brodsky JL, Madeo F, Gygi SP, Ashrafi K, Glickman MH, Rutter J.
Title A stress-responsive system for mitochondrial protein degradation.
Journal Mol Cell
Abstract We show that Ydr049 (renamed VCP/Cdc48-associated mitochondrial stress-responsive--Vms1), a member of an unstudied pan-eukaryotic protein family, translocates from the cytosol to mitochondria upon mitochondrial stress. Cells lacking Vms1 show progressive mitochondrial failure, hypersensitivity to oxidative stress, and decreased chronological life span. Both yeast and mammalian Vms1 stably interact with Cdc48/VCP/p97, a component of the ubiquitin/proteasome system with a well-defined role in endoplasmic reticulum-associated protein degradation (ERAD), wherein misfolded ER proteins are degraded in the cytosol. We show that oxidative stress triggers mitochondrial localization of Cdc48 and this is dependent on Vms1. When this system is impaired by mutation of Vms1, ubiquitin-dependent mitochondrial protein degradation, mitochondrial respiratory function, and cell viability are compromised. We demonstrate that Vms1 is a required component of an evolutionarily conserved system for mitochondrial protein degradation, which is necessary to maintain mitochondrial, cellular, and organismal viability.
Volume 40(3)
Pages 465-80
Published 2010-11-12
DOI 10.1016/j.molcel.2010.10.021
PII S1097-2765(10)00797-5
PMID 21070972
PMC PMC2998070
MeSH Adenosine Triphosphatases / metabolism Amino Acid Sequence Animals Caenorhabditis elegans / drug effects Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / metabolism Cell Cycle Proteins / metabolism Gene Deletion Humans Hydrogen Peroxide / pharmacology Longevity / drug effects Mice Microbial Viability / drug effects Mitochondria / drug effects Mitochondria / metabolism Mitochondrial Proteins / metabolism* Molecular Sequence Data Protein Binding / drug effects Protein Processing, Post-Translational* / drug effects Protein Transport / drug effects Saccharomyces cerevisiae / cytology Saccharomyces cerevisiae / metabolism Saccharomyces cerevisiae Proteins / chemistry Saccharomyces cerevisiae Proteins / metabolism Sirolimus / pharmacology Stress, Physiological* / drug effects Ubiquitin / metabolism Valosin Containing Protein
IF 15.584
Times Cited 192
C.elegans tm3229