Journal article
A Stress-Responsive System for Mitochondrial Protein Degradation
Molecular cell, Vol.40(3), pp.465-480
11/12/2010
DOI: 10.1016/j.molcel.2010.10.021
PMCID: PMC2998070
PMID: 21070972
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.
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► Vms1—an evolutionarily conserved protein that translocates to mitochondria under stress ► Loss of Vms1 causes progressive mitochondrial failure and cell death ► Vms1 binds to and causes the mitochondrial translocation of Cdc48 and Npl4 for protein degradation ► Vms1 is required for normal activity of the ubiquitin/proteasome system at mitochondria
Details
- Title: Subtitle
- A Stress-Responsive System for Mitochondrial Protein Degradation
- Creators
- Jin-Mi Heo - Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USANurit Livnat-Levanon - Department of Biology and The Russell Berrie Nanotechnology Institute, Technion, Israel Institute of Technology, 32000 Haifa, IsraelEric B Taylor - Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USAKevin T Jones - Department of Physiology and UCSF Diabetes Center, University of California, San Francisco, San Francisco, CA 94158-2517, USANoah Dephoure - Department of Cell Biology, Harvard University Medical School, Boston, MA 02115, USAJulia Ring - Department of Microbiology, Institute of Molecular Biosciences, Karl-Franzens-University of Graz, Graz, AustriaJianxin Xie - Cell Signaling Technology, Inc., Danvers, MA 01923, USAJeffrey L Brodsky - Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USAFrank Madeo - Department of Microbiology, Institute of Molecular Biosciences, Karl-Franzens-University of Graz, Graz, AustriaSteven P Gygi - Department of Cell Biology, Harvard University Medical School, Boston, MA 02115, USAKaveh Ashrafi - Department of Physiology and UCSF Diabetes Center, University of California, San Francisco, San Francisco, CA 94158-2517, USAMichael H Glickman - Department of Biology and The Russell Berrie Nanotechnology Institute, Technion, Israel Institute of Technology, 32000 Haifa, IsraelJared Rutter - Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
- Resource Type
- Journal article
- Publication Details
- Molecular cell, Vol.40(3), pp.465-480
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.molcel.2010.10.021
- PMID
- 21070972
- PMCID
- PMC2998070
- ISSN
- 1097-2765
- eISSN
- 1097-4164
- Language
- English
- Date published
- 11/12/2010
- Academic Unit
- Molecular Physiology and Biophysics
- Record Identifier
- 9984025673702771
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