Macroautophagy (herein referred to as autophagy) is an evolutionarily conserved mechanism of adaptation to adverse microenvironmental conditions, including limited nutrient supplies. Several sensors interacting with the autophagic machinery have evolved to detect fluctuations in key metabolic parameters. The signal transduction cascades operating downstream of these sensors are highly interconnected to control a spatially and chronologically coordinated autophagic response that maintains the health and function of individual cells while preserving organismal homeostasis. Here, we discuss the physiological regulation of autophagy by metabolic circuitries, as well as alterations of such control in disease.
