TOR complex 2-Ypk1 signaling maintains sphingolipid homeostasis by sensing and regulating ROS accumulation.
Reactive oxygen species (ROS) are produced during normal metabolism and can function as signaling molecules. However, ROS at elevated levels can damage cells. Here, we identify the conserved target of rapamycin complex 2 (TORC2)/Ypk1 signaling module as an important regulator of ROS in the model eukaryotic organism, S. cerevisiae. We show that TORC2/Ypk1 suppresses ROS produced both by mitochondria as well as by nonmitochondrial sources, including changes in acidification of the vacuole. Furthermore, we link vacuole-related ROS to sphingolipids, essential components of cellular membranes, whose synthesis is also controlled by TORC2/Ypk1 signaling. In total, our data reveal that TORC2/Ypk1 act within a homeostatic feedback loop to maintain sphingolipid levels and that ROS are a critical regulatory signal within this system. Thus, ROS sensing and signaling by TORC2/Ypk1 play a central physiological role in sphingolipid biosynthesis and in the maintenance of cell growth and viability.
Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, Davis, CA 95616, USA.
Brad J
BJ
Niles
Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, Davis, CA 95616, USA.
Amelia C
AC
Joslin
Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, Davis, CA 95616, USA.
Tara
T
Fresques
Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, Davis, CA 95616, USA. Electronic address: tpowers@ucdavis.edu.
Ted
T
Powers
D000143:Acids / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006706:Homeostasis; D042541:Intracellular Space / Q000378:metabolism; D000076225:Mechanistic Target of Rapamycin Complex 2; D050296:Microbial Viability; D008928:Mitochondria / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism
D000143:Acids; D046912:Multiprotein Complexes; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; C068124:MCK1 protein, S cerevisiae