title: 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.
authors.affiliation: Department of Molecular & Experimental Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: T Kelly
authors.initials: TK
authors.lastname: Rainbolt
authors.affiliation: Department of Molecular & Experimental Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Jaclyn M
authors.initials: JM
authors.lastname: Saunders
authors.affiliation: Department of Molecular & Experimental Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA wiseman@scripps.edu.
authors.forename: R Luke
authors.initials: RL
authors.lastname: Wiseman
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000255:Adenosine Triphosphate / Q000378:metabolism; D002460:Cell Line; D057809:HEK293 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018384:Oxidative Stress; D059748:Proteolysis
chemical_list: D024101:Mitochondrial Proteins; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D008666:Metalloendopeptidases; C410807:YME1L1 protein, human; C477817:molecule metalloprotease-related protein-1, human; D000074183:ATPases Associated with Diverse Cellular Activities
keywords: AAA protease; YME1L; mitochondrial proteostasis; oxidative stress