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

Authors

Iryna Bohovych, University of Nebraska- LincolnFollow
Stavroula Kastora, University of Aberdeen
Sara Christianson, University of Nebraska-Lincoln
Danelle Topil, University of Nebraska-Lincoln
Heejeong Kim, University of Nebraska-LincolnFollow
Teresa Fangman, University of Nebraska-Lincoln
You J. Zhou, University of Nebraska-LincolnFollow
Antoni Barrientos, University of Miami School of Medicine
Jaekwon Lee, University of Nebraska-LincolnFollow
Alistair J.P. Brown, University of Miami School of MedicineFollow
Oleh Khalimonchuk, University of Nebraska-LincolnFollow

Date of this Version

2016

Citation

Bohovych I, Kastora S, Christianson S, Topil D, Kim H, Fangman T, Zhou YJ, Barrientos A, Lee J, Brown AJP, Khalimonchuk O. 2016. Oma1 links mitochondrial protein quality control and TOR signaling to modulate physiological plasticity and cellular stress responses. Mol Cell Biol 36:2300 –2312.

Comments

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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.