Mitochondrial Import Efficiency of ATFS-1 Regulates Mitochondrial UPR Activation

Overview

Journal Science

Specialty Science

Date 2012 Jun 16

PMID 22700657

Citations 522

Authors

Amrita M Nargund

Mark W Pellegrino

Christopher J Fiorese

Brooke M Baker

Cole M Haynes

Affiliations

Soon will be listed here.

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.

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