The Matrix Peptide Exporter HAF-1 Signals a Mitochondrial UPR by Activating the Transcription Factor ZC376.7 in C. elegans Journal Article
| Authors: | Haynes, C. M.; Yang, Y.; Blais, S. P.; Neubert, T. A.; Ron, D. |
| Article Title: | The Matrix Peptide Exporter HAF-1 Signals a Mitochondrial UPR by Activating the Transcription Factor ZC376.7 in C. elegans |
| 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 (UPRmt). Here, we report that haf-1, a gene encoding a mitochondria-localized ATP-binding cassette protein, is required for signaling within the UPRmt and for coping with misfolded protein stress. Peptide efflux from isolated mitochondria was ATP dependent and required HAF-1 and the protease ClpP. Defective UPRmt 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 UPRmt. 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 UPRmt signaling across the mitochondrial inner membrane. © 2010 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; unclassified drug; nonhuman; proteins; animals; atp-binding cassette transporters; signaling; transcription factor; rna interference; transcription factors; abc transporter; cellbio; caenorhabditis elegans; adenosine triphosphate; protein folding; mitochondrial protein; mitochondria; mitochondrion; endopeptidase clp; mitochondrial proteins; caenorhabditis elegans proteins; unfolded protein response; protein hap 1; protein upr; transcription factor zc376.7 |
| Journal Title: | Molecular Cell |
| Volume: | 37 |
| Issue: | 4 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2010-02-26 |
| Start Page: | 529 |
| End Page: | 540 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2010.01.015 |
| PUBMED: | 20188671 |
| PROVIDER: | scopus |
| PMCID: | PMC2846537 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 5" - "Export Date: 20 April 2011" - "CODEN: MOCEF" - "Source: Scopus" |
