A mitochondrial specific stress response in mammalian cells

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...

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Bibliographic Details
Published in:	The EMBO journal Vol. 21; no. 17; pp. 4411 - 4419
Main Authors:	Zhao, Quan, Wang, Jianghui, Levichkin, Ilya V., Stasinopoulos, Stan, Ryan, Michael T., Hoogenraad, Nicholas J.
Format:	Journal Article
Language:	English
Published:	Chichester, UK John Wiley & Sons, Ltd 02-09-2002 Blackwell Publishing Ltd Oxford University Press
Subjects:	Adenosine Triphosphatases - biosynthesis Adenosine Triphosphatases - genetics Animals CCAAT-Enhancer-Binding Proteins - genetics CCAAT-Enhancer-Binding Proteins - physiology Cell Nucleus - metabolism Cercopithecus aethiops Chaperonin 10 - biosynthesis Chaperonin 10 - genetics Chaperonin 60 - biosynthesis Chaperonin 60 - genetics COS Cells Endopeptidase Clp Gene Expression Regulation gene regulation Genes, Dominant Heat-Shock Proteins - biosynthesis Heat-Shock Proteins - genetics HSP40 Heat-Shock Proteins Mammals mitochondria Mitochondria - physiology molecular chaperones Ornithine Carbamoyltransferase - chemistry Ornithine Carbamoyltransferase - genetics Ornithine Carbamoyltransferase - metabolism Promoter Regions, Genetic Protein Folding Protein Processing, Post-Translational Protein Transport Proteins Recombinant Fusion Proteins - physiology Regulatory Sequences, Nucleic Acid Sequence Deletion Serine Endopeptidases - biosynthesis Serine Endopeptidases - genetics Signal Transduction stress Stress, Physiological - genetics Stress, Physiological - physiopathology Transcription Factor CHOP Transcription Factors - genetics Transcription Factors - physiology Transcription, Genetic Transfection
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Summary:	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/EBPβ, regulates expression of mitochondrial stress genes in response to the accumulation of unfolded proteins.
Bibliography:	ArticleID:EMBJ7594664 istex:3F5030A1D89AA8C6F41A9389CB34820914F676CD ark:/67375/WNG-3VX3W3QV-J ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0261-4189 1460-2075 1460-2075
DOI:	10.1093/emboj/cdf445