Stress-regulated translational attenuation adapts mitochondrial protein import through Tim17A degradation.

Stress-regulated signaling pathways protect mitochondrial proteostasis and function from pathologic insults. Despite the importance of stress-regulated signaling pathways in mitochondrial proteome maintenance, the molecular mechanisms by which these pathways maintain mitochondrial proteostasis remain largely unknown. We identify Tim17A as a stress-regulated subunit of the translocase of the inner membrane 23 (TIM23) mitochondrial protein import complex. We show that Tim17A protein levels are decreased downstream of stress-regulated translational attenuation induced by eukaryotic initiation factor 2α (eIF2α) phosphorylation through a mechanism dependent on the mitochondrial protease YME1L. Furthermore, we demonstrate that decreasing Tim17A attenuates TIM23-dependent protein import, promotes the induction of mitochondrial unfolded protein response (UPR)-associated proteostasis genes, and confers stress resistance in C. elegans and mammalian cells. Thus, our results indicate that Tim17A degradation is a stress-responsive mechanism by which cells adapt mitochondrial protein import efficiency and promote mitochondrial proteostasis in response to the numerous pathologic insults that induce stress-regulated translation attenuation. Copyright © 2013 Elsevier Inc. All rights reserved.

Citation

T Kelly Rainbolt, Neli Atanassova, Joseph C Genereux, R Luke Wiseman. Stress-regulated translational attenuation adapts mitochondrial protein import through Tim17A degradation. Cell metabolism. 2013 Dec 03;18(6):908-19

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PMID: 24315374

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