RRC ID 3581
Author Haynes CM, Petrova K, Benedetti C, Yang Y, Ron D.
Title ClpP mediates activation of a mitochondrial unfolded protein response in C. elegans.
Journal Dev. Cell
Abstract The cellular response to unfolded and misfolded proteins in the mitochondrial matrix is poorly understood. Here, we report on a genome-wide RNAi-based screen for genes that signal the mitochondrial unfolded protein response (UPR(mt)) in C. elegans. Unfolded protein stress in the mitochondria correlates with complex formation between a homeodomain-containing transcription factor DVE-1 and the small ubiquitin-like protein UBL-5, both of which are encoded by genes required for signaling the UPR(mt). Activation of the UPR(mt) correlates temporally and spatially with nuclear redistribution of DVE-1 and with its enhanced binding to the promoters of mitochondrial chaperone genes. These events and the downstream UPR(mt) are attenuated in animals with reduced activity of clpp-1, which encodes a mitochondrial matrix protease homologous to bacterial ClpP. As ClpP is known to function in the bacterial heat-shock response, our findings suggest that eukaryotes utilize component(s) from the protomitochondrial symbiont to signal the UPR(mt).
Volume 13(4)
Pages 467-80
Published 2007-10
DOI 10.1016/j.devcel.2007.07.016
PII S1534-5807(07)00277-8
PMID 17925224
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / embryology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Nucleus / metabolism Embryo, Nonmammalian Endopeptidase Clp / genetics Endopeptidase Clp / metabolism* Escherichia coli Proteins / genetics Genome, Helminth Mitochondria / metabolism* Molecular Chaperones / genetics Molecular Chaperones / metabolism Mutation Promoter Regions, Genetic Protein Folding* Signal Transduction Transcription Factors / metabolism* Ubiquitins / genetics Ubiquitins / metabolism*
IF 9.19
Times Cited 170
C.elegans tm259