RRC ID 46605
著者 Haynes CM, Yang Y, Blais SP, Neubert TA, Ron D.
タイトル The matrix peptide exporter HAF-1 signals a mitochondrial UPR by activating the transcription factor ZC376.7 in C. elegans.
ジャーナル Mol Cell
Abstract Genetic analyses previously implicated the matrix-localized protease ClpP in signaling the stress of protein misfolding in the mitochondrial matrix to activate nuclear-encoded mitochondrial chaperone genes in C. elegans (UPR(mt)). Here, we report that haf-1, a gene encoding a mitochondria-localized ATP-binding cassette protein, is required for signaling within the UPR(mt) and for coping with misfolded protein stress. Peptide efflux from isolated mitochondria was ATP dependent and required HAF-1 and the protease ClpP. Defective UPR(mt) signaling in the haf-1-deleted worms was associated with failure of the bZIP protein, ZC376.7, to localize to nuclei in worms with perturbed mitochondrial protein folding, whereas zc376.7(RNAi) strongly inhibited the UPR(mt). These observations suggest a simple model whereby perturbation of the protein-folding environment in the mitochondrial matrix promotes ClpP-mediated generation of peptides whose haf-1-dependent export from the matrix contributes to UPR(mt) signaling across the mitochondrial inner membrane.
巻・号 37(4)
ページ 529-40
公開日 2010-2-26
DOI 10.1016/j.molcel.2010.01.015
PII S1097-2765(10)00044-4
PMID 20188671
PMC PMC2846537
MeSH ATP-Binding Cassette Transporters / genetics ATP-Binding Cassette Transporters / metabolism* Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Mitochondria / metabolism* Mitochondrial Proteins / metabolism Protein Folding RNA Interference Signal Transduction* Transcription Factors / genetics Transcription Factors / metabolism* Unfolded Protein Response*
IF 15.584
引用数 272
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
線虫 tm843 tm2183 tm1920