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PMID: 12198143 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A mitochondrial specific stress response in mammalian cells.

The EMBO journal ·Vol. 21 ·No. 17 ·2002-09-02 ·Pages 4411-9

Zhao Q, Wang J, Levichkin IV, Stasinopoulos S, Ryan MT, Hoogenraad NJ

Abstract

Cells respond to a wide variety of stresses through the transcriptional activation of genes that harbour stress elements within their promoters. While many of these elements are shared by genes encoding proteins representative of all subcellular compartments, cells can also respond to stresses that are specific to individual organelles, such as the endoplasmic reticulum un folded protein response. Here we report on the discovery and characterization of a mitochondrial stress response in mammalian cells. We find that the accumulation of unfolded protein within the mitochondrial matrix results in the transcriptional upregulation of nuclear genes encoding mitochondrial stress proteins such as chaperonin 60, chaperonin 10, mtDnaJ and ClpP, but not those encoding stress proteins of the endoplasmic reticulum. Analysis of the chaperonin 60/10 bidirectional promoter identified a CHOP element as the mitochondrial stress response element. Dominant-negative mutant forms of CHOP and overexpression of CHOP revealed that this transcription factor, in association with C/EBPbeta, regulates expression of mitochondrial stress genes in response to the accumulation of unfolded proteins.

MeSH Terms
Adenosine Triphosphatases/biosynthesis,genetics Animals CCAAT-Enhancer-Binding Proteins/genetics,physiology COS Cells Cell Nucleus/metabolism Chaperonin 10/biosynthesis,genetics Chaperonin 60/biosynthesis,genetics Chlorocebus aethiops Endopeptidase Clp Gene Expression Regulation Genes, Dominant HSP40 Heat-Shock Proteins Heat-Shock Proteins/biosynthesis,genetics Mitochondria/physiology Ornithine Carbamoyltransferase/chemistry,genetics,metabolism Promoter Regions, Genetic Protein Folding Protein Processing, Post-Translational Protein Transport Recombinant Fusion Proteins/physiology Regulatory Sequences, Nucleic Acid Sequence Deletion Serine Endopeptidases/biosynthesis,genetics Signal Transduction Stress, Physiological/genetics,physiopathology Transcription Factor CHOP Transcription Factors/genetics,physiology Transcription, Genetic Transfection
Chemicals
CCAAT-Enhancer-Binding Proteins Chaperonin 10 Chaperonin 60 HSP40 Heat-Shock Proteins Heat-Shock Proteins Recombinant Fusion Proteins Transcription Factors Transcription Factor CHOP Ornithine Carbamoyltransferase Serine Endopeptidases Endopeptidase Clp Adenosine Triphosphatases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Zhao Quan
Department of Biochemistry, La Trobe University, Melbourne, Victoria 3086, Australia.
Wang Jianghui
Levichkin Ilya V
Stasinopoulos Stan
Ryan Michael T
Hoogenraad Nicholas J
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdf445
Published
2002-09-02
Pages
4411-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC126185
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdf445 PMC Full Text View journal details
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