Oma1 links mitochondrial protei quality control and TOR signaling to modulaten physiological plasticity and cellular stress responses

Iryna Bohovych, Stavroula Kastor, Sara Christianson, Danelle Topil, Heejeong Kim, Teresa Fangman, You J. Zhou, Antonio Barrientos, Jaekwon Lee, Alistair J P Brown, Oleh Khalimonchuk

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12 Scopus citations

Abstract

A network of conserved proteases known as the intramitochondrial quality control (IMQC) system is central to mitochondrial protein homeostasis and cellular health. IMQC proteases also appear to participate in establishment of signaling cues for mitochondrion- to-nucleus communication. However, little is known about this process. Here, we show that in Saccharomyces cerevisiae, inactivation of the membrane-bound IMQC protease Oma1 interferes with oxidative-stress responses through enhanced production of reactive oxygen species (ROS) during logarithmic growth and reduced stress signaling via the TORC1-Rim15- Msn2/Msn4 axis. Pharmacological or genetic prevention of ROS accumulation in Oma1-deficient cells restores this defective TOR signaling. Additionally, inactivation of the Oma1 ortholog in the human fungal pathogen Candida albicans also alters TOR signaling and, unexpectedly, leads to increased resistance to neutrophil killing and virulence in the invertebrate animal model Galleria mellonella. Our findings reveal a novel and evolutionarily conserved link between IMQC and TOR-mediated signaling that regulates physiological plasticity and pancellular oxidative-stress responses.

Original languageEnglish (US)
Pages (from-to)2300-2312
Number of pages13
JournalMolecular and Cellular Biology
Volume36
Issue number17
DOIs
StatePublished - 2016

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Bohovych, I., Kastor, S., Christianson, S., Topil, D., Kim, H., Fangman, T., Zhou, Y. J., Barrientos, A., Lee, J., Brown, A. J. P., & Khalimonchuk, O. (2016). Oma1 links mitochondrial protei quality control and TOR signaling to modulaten physiological plasticity and cellular stress responses. Molecular and Cellular Biology, 36(17), 2300-2312. https://doi.org/10.1128/MCB.00156-16