ClpP mediates activation of a mitochondrial unfolded protein response in C. elegans.
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).
Haynes
Cole M
CM
Kimmel Center for Biology and Medicine of Skirball Institute and Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
Petrova
Kseniya
K
Benedetti
Cristina
C
Yang
Yun
Y
Ron
David
D
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004625:Embryo, Nonmammalian; D049071:Endopeptidase Clp / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics; D049751:Genome, Helminth; D008928:Mitochondria / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011401:Promoter Regions, Genetic; D017510:Protein Folding; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D014157:Transcription Factors; D014452:Ubiquitins; C515527:Ubl-5 protein, C elegans; C483572:ClpP protease, E coli; D049071:Endopeptidase Clp