Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation Journal Article
| Authors: | Nargund, A. M.; Pellegrino, M. W.; Fiorese, C. J.; Baker, B. M.; Haynes, C. M. |
| Article Title: | Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation |
| Abstract: | To better understand the response to mitochondrial dysfunction, we examined the mechanism by which ATFS-1 (activating transcription factor associated with stress-1) senses mitochondrial stress and communicates with the nucleus during the mitochondrial unfolded protein response (UPR mt) in Caenorhabditis elegans. We found that the key point of regulation is the mitochondrial import efficiency of ATFS-1. In addition to a nuclear localization sequence, ATFS-1 has an N-terminal mitochondrial targeting sequence that is essential for UPR mt repression. Normally, ATFS-1 is imported into mitochondria and degraded. However, during mitochondrial stress, we found that import efficiency was reduced, allowing a percentage of ATFS-1 to accumulate in the cytosol and traffic to the nucleus. Our results show that cells monitor mitochondrial import efficiency via ATFS-1 to coordinate the level of mitochondrial dysfunction with the protective transcriptional response. |
| Keywords: | unclassified drug; nonhuman; protein localization; animals; gene expression; stress, physiological; protein; transcription, genetic; wild type; transcription factors; gene expression regulation; amino terminal sequence; molecular analysis; active transport, cell nucleus; stress; caenorhabditis elegans; cell nucleus; mitochondria; mitochondrion; cytosol; nuclear localization signals; nematode; disorders of mitochondrial functions; caenorhabditis elegans proteins; unfolded protein response; activating transcription factor associated with stress 1 |
| Journal Title: | Science |
| Volume: | 337 |
| Issue: | 6094 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2012-08-03 |
| Start Page: | 587 |
| End Page: | 590 |
| Language: | English |
| DOI: | 10.1126/science.1223560 |
| PROVIDER: | scopus |
| PUBMED: | 22700657 |
| PMCID: | PMC3518298 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 September 2012" - "CODEN: SCIEA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work