Autophagy regulation by signaling

The first identified regulators of autophagy were the hormones Glucagon and Insulin, long before the recognition that they act through receptor-mediated cell signaling pathways. More than two decades since the identification of the autophagy molecular machinery, we appreciate that regulation of autophagy is complex, operates at several levels, and serves many functions to maintain cellular and organismal health. TORC1 remains the best-defined gatekeeper, serving to sense nutrient and energy sufficiency while also integrating systemic growth factor signaling to control cell growth and autophagy autonomously. This review summarizes the current understanding of autophagy regulation by signaling through TORC1-dependent and independent mechanisms and discusses the emerging understanding of control and coordinated response of autophagy at the organism level.