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YME1L degradation reduces mitochondrial proteolytic capacity during oxidative stress.


ABSTRACT: Mitochondrial proteostasis is maintained by a network of ATP-dependent quality control proteases including the inner membrane protease YME1L. Here, we show that YME1L is a stress-sensitive mitochondrial protease that is rapidly degraded in response to acute oxidative stress. This degradation requires reductions in cellular ATP and involves the activity of the ATP-independent protease OMA1. Oxidative stress-dependent reductions in YME1L inhibit protective YME1L-dependent functions and increase cellular sensitivity to oxidative insult. Collectively, our results identify stress-induced YME1L degradation as a biologic process that attenuates protective regulation of mitochondrial proteostasis and promotes cellular death in response to oxidative stress.

SUBMITTER: Rainbolt TK 

PROVIDER: S-EPMC4304733 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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YME1L degradation reduces mitochondrial proteolytic capacity during oxidative stress.

Rainbolt T Kelly TK   Saunders Jaclyn M JM   Wiseman R Luke RL  

EMBO reports 20141127 1


Mitochondrial proteostasis is maintained by a network of ATP-dependent quality control proteases including the inner membrane protease YME1L. Here, we show that YME1L is a stress-sensitive mitochondrial protease that is rapidly degraded in response to acute oxidative stress. This degradation requires reductions in cellular ATP and involves the activity of the ATP-independent protease OMA1. Oxidative stress-dependent reductions in YME1L inhibit protective YME1L-dependent functions and increase ce  ...[more]

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