Oma1 Links Mitochondrial Protein Quality Control and TOR Signaling To Modulate Physiological Plasticity and Cellular Stress Responses

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

Research output: Contribution to journalArticle

12 Citations (Scopus)
3 Downloads (Pure)

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
Pages (from-to)2300-2312
Number of pages13
JournalMolecular and Cellular Biology
Volume36
Issue number17
Early online date20 Jun 2016
DOIs
Publication statusPublished - Sep 2016

    Fingerprint

Cite this

Bohovych, I., Kastora, 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 Protein Quality Control and TOR Signaling To Modulate Physiological Plasticity and Cellular Stress Responses. Molecular and Cellular Biology, 36(17), 2300-2312. https://doi.org/10.1128/MCB.00156-16