TOR complex 2-Ypk1 signaling is an essential positive regulator of the general amino acid control response and autophagy.

Ariadne Vlahakis, Martin Graef, Jodi Nunnari, Ted Powers

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The highly conserved Target of Rapamycin (TOR) kinase is a central regulator of cell growth and metabolism in response to nutrient availability. TOR functions in two structurally and functionally distinct complexes, TOR Complex 1 (TORC1) and TOR Complex 2 (TORC2). Through TORC1, TOR negatively regulates autophagy, a conserved process that functions in quality control and cellular homeostasis and, in this capacity, is part of an adaptive nutrient deprivation response. Here we demonstrate that during amino acid starvation TOR also operates independently as a positive regulator of autophagy through the conserved TORC2 and its downstream target protein kinase, Ypk1. Under these conditions, TORC2-Ypk1 signaling negatively regulates the Ca(2+)/calmodulin-dependent phosphatase, calcineurin, to enable the activation of the amino acid-sensing eIF2α kinase, Gcn2, and to promote autophagy. Our work reveals that the TORC2 pathway regulates autophagy in an opposing manner to TORC1 to provide a tunable response to cellular metabolic status.

Original languageEnglish (US)
Pages (from-to)10586-10591
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number29
DOIs
StatePublished - 2014

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Autophagy
Sirolimus
Amino Acids
Phosphotransferases
Aminoacylation
Food
Calmodulin
Starvation
Quality Control
Protein Kinases
Homeostasis
TOR complex 2
Growth
mechanistic target of rapamycin complex 1

ASJC Scopus subject areas

  • General

Cite this

TOR complex 2-Ypk1 signaling is an essential positive regulator of the general amino acid control response and autophagy. / Vlahakis, Ariadne; Graef, Martin; Nunnari, Jodi; Powers, Ted.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 29, 2014, p. 10586-10591.

Research output: Contribution to journalArticle

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