TOR Complex 2-Ypk1 signaling maintains sphingolipid homeostasis by sensing and regulating ROS accumulation

Brad J. Niles, Amelia C. Joslin, Tara Fresques, Ted Powers

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)541-552
Number of pages12
JournalCell Reports
Volume6
Issue number3
DOIs
StatePublished - Feb 13 2014

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Sphingolipids
Reactive Oxygen Species
Homeostasis
Vacuoles
Mitochondria
Acidification
Biosynthesis
Cell growth
TOR complex 2
Metabolism
Saccharomyces cerevisiae
Cell Survival
Maintenance
Membranes
Feedback
Molecules
Growth

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

TOR Complex 2-Ypk1 signaling maintains sphingolipid homeostasis by sensing and regulating ROS accumulation. / Niles, Brad J.; Joslin, Amelia C.; Fresques, Tara; Powers, Ted.

In: Cell Reports, Vol. 6, No. 3, 13.02.2014, p. 541-552.

Research output: Contribution to journalArticle

Niles, Brad J. ; Joslin, Amelia C. ; Fresques, Tara ; Powers, Ted. / TOR Complex 2-Ypk1 signaling maintains sphingolipid homeostasis by sensing and regulating ROS accumulation. In: Cell Reports. 2014 ; Vol. 6, No. 3. pp. 541-552.
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