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

被引：16

作者：

Bohovych, Iryna ^{[1
,2
]}

Kastora, Stavroula ^{[3
]}

Christianson, Sara ^{[1
]}

Topil, Danelle ^{[1
]}

Kim, Heejeong ^{[1
,2
]}

Fangman, Teresa ^{[2
]}

Zhou, You J. ^{[2
]}

Barrientos, Antoni ^{[4
,5
]}

Lee, Jaekwon ^{[1
,2
]}

Brown, Alistair J. P. ^{[3
]}

Khalimonchuk, Oleh ^{[1
,2
]}

机构：

[1] Univ Nebraska Lincoln, Dept Biochem, Lincoln, NE 68588 USA

[2] Univ Nebraska Lincoln, Redox Biol Ctr, Lincoln, NE 68588 USA

[3] Univ Aberdeen, Sch Med Sci, Foresterhill, Aberdeen, Scotland

[4] Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL USA

[5] Univ Miami, Sch Med, Dept Neurol, Miami, FL USA

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2016年 / 36卷 / 17期

基金：

英国生物技术与生命科学研究理事会; 美国国家卫生研究院; 欧洲研究理事会; 英国医学研究理事会;

关键词：

CHRONOLOGICAL LIFE-SPAN; PATHOGEN CANDIDA-ALBICANS; SACCHAROMYCES-CEREVISIAE; NUCLEAR-LOCALIZATION; CALORIC RESTRICTION; TRANSCRIPTIONAL RESPONSE; METALLOPROTEASE OMA1; YEAST; KINASE; H2O2;

D O I：

10.1128/MCB.00156-16

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2300 / 2312

页数：13

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[1] Proteolytic control of mitochondrial function and morphogenesis [J].