title: Reciprocal Degradation of YME1L and OMA1 Adapts Mitochondrial Proteolytic Activity during Stress.
abstract: The mitochondrial inner membrane proteases YME1L and OMA1 are critical regulators of essential mitochondrial functions, including inner membrane proteostasis maintenance and mitochondrial dynamics. Here, we show that YME1L and OMA1 are reciprocally degraded in response to distinct types of cellular stress. OMA1 is degraded through a YME1L-dependent mechanism in response to toxic insults that depolarize the mitochondrial membrane. Alternatively, insults that depolarize mitochondria and deplete cellular ATP stabilize active OMA1 and promote YME1L degradation. We show that the differential degradation of YME1L and OMA1 alters their proteolytic processing of the dynamin-like GTPase OPA1, a critical regulator of mitochondrial inner membrane morphology, which influences the recovery of tubular mitochondria following membrane-depolarization-induced fragmentation. Our results reveal the differential stress-induced degradation of YME1L and OMA1 as a mechanism for sensitively adapting mitochondrial inner membrane protease activity and function in response to distinct types of cellular insults.
authors.affiliation: Department of Molecular and Experimental Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: T Kelly
authors.initials: TK
authors.lastname: Rainbolt
authors.affiliation: Department of Molecular and Experimental Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Justine
authors.initials: J
authors.lastname: Lebeau
authors.affiliation: Department of Molecular and Experimental Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Puchades
authors.affiliation: Department of Molecular and Experimental Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: 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; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008666:Metalloendopeptidases / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins; D010447:Peptide Hydrolases / Q000378:metabolism; D059748:Proteolysis
chemical_list: D024101:Mitochondrial Proteins; D000255:Adenosine Triphosphate; D010447:Peptide Hydrolases; D008666:Metalloendopeptidases; C410807:YME1L1 protein, human; C477817:molecule metalloprotease-related protein-1, human; D000074183:ATPases Associated with Diverse Cellular Activities