非表示:
キーワード:
Amino Acids/*pharmacology
Autophagy/*drug effects
Calcineurin/metabolism
Glycogen Synthase Kinase 3/*metabolism
Models, Biological
Multiprotein Complexes/*metabolism
Saccharomyces cerevisiae/cytology/*enzymology
Saccharomyces cerevisiae Proteins/*metabolism
Signal Transduction/*drug effects
TOR Serine-Threonine Kinases/*metabolism
Atg8
Gcn4
要旨:
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 eIF2alpha 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.
