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Real-time Monitoring of Mitochondrial Respiration in Cytokine-differentiated Human Primary T Cells
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Mitochondrial respiration links TOR complex 2 signaling to calcium regulation and autophagy

Ariadne Vlahakis1, Nerea Lopez Muniozguren1, Ted Powers1

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

Autophagy
|March 22, 2017
PubMed

Insights

Target of rapamycin complex 2 (TORC2) controls autophagy by regulating mitochondrial respiration and calcium signaling. This pathway involves Mid1, a key activator of calcineurin, linking TORC2 to cellular stress responses.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The target of rapamycin (TOR) kinase regulates cell growth and is found in two complexes: TORC1 and TORC2.
  • TORC2 positively influences autophagy, a cellular degradation process, particularly during amino acid starvation.
  • TORC2 signaling normally inhibits calcineurin, a calcium-regulated phosphatase, to promote the general amino acid control (GAAC) response and autophagy.

Purpose of the Study:

  • To elucidate the novel regulatory mechanism by which TORC2 controls autophagy.
  • To investigate the role of mitochondrial respiration and calcium homeostasis in TORC2-mediated autophagy.
  • To identify upstream activators of calcineurin in the context of TORC2 signaling.

Main Methods:

  • Investigated the interplay between TORC2 signaling, mitochondrial function, and autophagy.
  • Analyzed the regulation of calcineurin activity by mitochondrial respiration.
  • Examined the function of the calcium channel regulatory protein Mid1 in calcineurin activation.

Main Results:

  • Demonstrated that TORC2 regulates calcineurin activity through modulation of mitochondrial respiratory activity.
  • Identified mitochondrial oxidative stress as a key factor influencing Mid1.
  • Showed that Mid1 is an essential upstream activator of calcineurin.

Conclusions:

  • Discovered a novel regulatory pathway for autophagy involving TORC2, mitochondrial respiration, and calcium homeostasis.
  • Established a link between mitochondrial oxidative stress, Mid1, and calcineurin activity.
  • Provided new insights into the complex regulation of autophagy and cellular stress responses.
Keywords:
GAACMid1TORC1TORC2Ypk1amino acidcalcineurincalciumendoplasmic reticulummitochondriareactive oxygen species (ROS)

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