Overview of Autophagy and Its Molecular Regulation

Renewable nutrient utilization and maintenance of metabolic homeostasis are key events to retain the normal function of cells or the whole body. As the center of nutrient and organelle recycling, autophagy, the cell “self-digestion” process, plays an important role in sensing and responding to the dynamic changes of the energy status and amino acid pool in an organism. The basic autophagy process consists of phagophore initiation, autophagosome formation and maturation, and fusion with the lysosome. In response to starvation or stress conditions, phagophore initiation requires many autophagy-related genes (ATGs) including PI3KC3 and ULK1 gene complexes. Autophagosome engulfs the cargo by extension and closure of its membrane, followed by fusion with the lysosome to degrade the cargo for reuse or clearance. Several groups of proteins mediate the fusion of autophagosome and lysosome, such as SNAREs and HOPs. The autophagy proteins are regulated by the energy sensor AMP-activated protein kinase and the mammalian mechanistic target of rapamycin complex 1, which are metabolic core kinases and important in nutrient signaling. Upon cellular stress, autophagy is induced as the stress sensor downstream and initiator of cytoplasmic component recycling. Understanding the interactions of autophagy with nutrient deficiency and cellular stress, as well as the associated signaling pathways, will provide new information on the prevention of metabolic disease and related role of nutrition.