Stress-triggered Activation of the Metalloprotease Oma1 Involves its C-terminal Region and is Important for Mitochondrial Stress Protection in Yeast [Cell Biology]

March 19th, 2014 by Bohovych, I., Donaldson, G., Christianson, S., Zahayko, N., Khalimonchuk, O.

Functional integrity of mitochondria is critical for optimal cellular physiology. A suite of conserved mitochondrial proteases known as intramitochondrial quality control (IMQC) represents one of the mechanisms assuring normal mitochondrial function. We previously demonstrated that ATP-independent metalloprotease Oma1 mediates degradation of hypo-hemylated Cox1 subunit of cytochrome c oxidase (CcO) and is active in CcO-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 IMQC components.
  • Posted in Journal of Biological Chemistry, Publications
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