YME1L degradation reduces mitochondrial proteolytic capacity during oxidative stress

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.