Mitochondrial respiration links TOR complex 2 signaling to calcium regulation and autophagy.
The target of rapamycin (TOR) kinase is a conserved regulator of cell growth and functions within 2 different protein complexes, TORC1 and TORC2, where TORC2 positively controls macroautophagy/autophagy during amino acid starvation. Under these conditions, TORC2 signaling inhibits the activity of the calcium-regulated phosphatase calcineurin and promotes the general amino acid control (GAAC) response and autophagy. Here we demonstrate that TORC2 regulates calcineurin by controlling the respiratory activity of mitochondria. In particular, we find that mitochondrial oxidative stress affects the calcium channel regulatory protein Mid1, which we show is an essential upstream activator of calcineurin. Thus, these findings describe a novel regulation for autophagy that involves TORC2 signaling, mitochondrial respiration, and calcium homeostasis.
a Department of Molecular and Cellular Biology , College of Biological Sciences, University of California , Davis , CA , USA.
Ariadne
A
Vlahakis
a Department of Molecular and Cellular Biology , College of Biological Sciences, University of California , Davis , CA , USA.
Nerea
N
Lopez Muniozguren
a Department of Molecular and Cellular Biology , College of Biological Sciences, University of California , Davis , CA , USA.
Ted
T
Powers
D001343:Autophagy; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D019069:Cell Respiration; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000076225:Mechanistic Target of Rapamycin Complex 2 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction
C090463:MID1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; D000076225:Mechanistic Target of Rapamycin Complex 2; D038362:Glycogen Synthase Kinase 3; C068124:MCK1 protein, S cerevisiae; D019703:Calcineurin; D002118:Calcium
GAAC; Mid1; TORC1; TORC2; Ypk1; amino acid; calcineurin; calcium; endoplasmic reticulum; mitochondria; reactive oxygen species (ROS)