title: Stress-triggered activation of the metalloprotease Oma1 involves its C-terminal region and is important for mitochondrial stress protection in yeast.
abstract: Functional integrity of mitochondria is critical for optimal cellular physiology. A suite of conserved mitochondrial proteases known as intramitochondrial quality control represents one of the mechanisms assuring normal mitochondrial function. We previously demonstrated that ATP-independent metalloprotease Oma1 mediates degradation of hypohemylated Cox1 subunit of cytochrome c oxidase and is active in cytochrome c oxidase-deficient mitochondria. Here we show that Oma1 is important for adaptive responses to various homeostatic insults and preservation of normal mitochondrial function under damage-eliciting conditions. Changes in membrane potential, oxidative stress, or chronic hyperpolarization lead to increased Oma1-mediated proteolysis. The stress-triggered induction of Oma1 proteolytic activity appears to be associated with conformational changes within the Oma1 homo-oligomeric complex, and these alterations likely involve C-terminal residues of the protease. Substitutions in the conserved C-terminal region of Oma1 impair its ability to form a labile proteolytically active complex in response to stress stimuli. We demonstrate that Oma1 genetically interacts with other inner membrane-bound quality control proteases. These findings indicate that yeast Oma1 is an important player in IM protein homeostasis and integrity by acting in concert with other intramitochondrial quality control components.
authors.affiliation: From the Department of Biochemistry and Nebraska Redox Biology Center, University of Nebraska-Lincoln, Lincoln, Nebraska 68588.
authors.forename: Iryna
authors.initials: I
authors.lastname: Bohovych
authors.forename: Garrett
authors.initials: G
authors.lastname: Donaldson
authors.forename: Sara
authors.initials: S
authors.lastname: Christianson
authors.forename: Nataliya
authors.initials: N
authors.lastname: Zahayko
authors.forename: Oleh
authors.initials: O
authors.lastname: Khalimonchuk
mesh_terms: D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C526453:Cox1 protein, S cerevisiae; D003576:Electron Transport Complex IV; D045726:Metalloproteases; C480741:Oma1 protein, S cerevisiae
keywords: Genetics; Metalloprotease; Mitochondria; Mitochondrial Stress; Oma1; Oxidative Stress; Proteases; Yeast