Stress-triggered activation of the metalloprotease Oma1 involves its C-terminal region and is important for mitochondrial stress protection in yeast

Iryna Bohovych, Garrett Donaldson, Sara Christianson, Nataliya Zahayko, Oleh Khalimonchuk

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)13259-13272
Number of pages14
JournalJournal of Biological Chemistry
Volume289
Issue number19
DOIs
StatePublished - Jan 1 2014

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Metalloproteases
Quality Control
Yeast
Quality control
Mitochondria
Peptide Hydrolases
Yeasts
Chemical activation
Electron Transport Complex IV
Proteolysis
Membranes
Oxidative stress
Physiology
Membrane Potentials
Oxidative Stress
Homeostasis
Substitution reactions
Adenosine Triphosphate
Degradation
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Stress-triggered activation of the metalloprotease Oma1 involves its C-terminal region and is important for mitochondrial stress protection in yeast. / Bohovych, Iryna; Donaldson, Garrett; Christianson, Sara; Zahayko, Nataliya; Khalimonchuk, Oleh.

In: Journal of Biological Chemistry, Vol. 289, No. 19, 01.01.2014, p. 13259-13272.

Research output: Contribution to journalArticle

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