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

Brad J Niles1, Amelia C Joslin1, Tara Fresques1

  • 1Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, Davis, CA 95616, USA.

Cell Reports
|January 28, 2014
PubMed

Insights

The TORC2/Ypk1 signaling pathway regulates reactive oxygen species (ROS) in yeast. This pathway maintains sphingolipid levels, crucial for cell growth and viability, by controlling ROS production.

Area of Science:

  • Cellular Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Reactive oxygen species (ROS) are key signaling molecules in cellular metabolism.
  • Elevated ROS levels can lead to cellular damage.
  • The conserved target of rapamycin complex 2 (TORC2)/Ypk1 pathway is implicated in cellular regulation.

Purpose of the Study:

  • To investigate the role of the TORC2/Ypk1 signaling module in regulating ROS production.
  • To elucidate the connection between ROS, vacuole function, and sphingolipid biosynthesis.
  • To understand the homeostatic feedback mechanisms involving ROS and sphingolipids.

Main Methods:

  • Utilized the model organism S. cerevisiae.
  • Investigated ROS production from both mitochondrial and non-mitochondrial sources.
  • Analyzed the impact of vacuole acidification on ROS.
  • Examined the regulation of sphingolipid synthesis by TORC2/Ypk1.

Main Results:

  • Identified TORC2/Ypk1 as a conserved regulator of ROS.
  • Demonstrated that TORC2/Ypk1 suppresses ROS from mitochondrial and non-mitochondrial sources, including vacuole acidification.
  • Linked vacuole-related ROS to sphingolipids, whose synthesis is controlled by TORC2/Ypk1.
  • Revealed a homeostatic feedback loop where TORC2/Ypk1 maintains sphingolipid levels via ROS signaling.

Conclusions:

  • TORC2/Ypk1 signaling is critical for controlling ROS homeostasis.
  • ROS act as a vital signal in the TORC2/Ypk1-mediated regulation of sphingolipid biosynthesis.
  • This regulatory system is essential for maintaining cell growth and viability.

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