Molecular regulation of autophagy machinery by mTOR-dependent and -independent pathways

Macroautophagy is a lysosomal degradative pathway or recycling process that maintains cellular homeostasis. This autophagy involves a series of sequential processing events, such as initiation; elongation and nucleation of the isolation membrane; cargo recruitment and maturation of the autophagosome (AP); transport of the AP; docking and fusion of the AP with a late endosome or lysosome; and regeneration of the lysosome by the autophagic lysosomal reformation cycle. These events are critically coordinated by the action of a set of several key components, including autophagy-related proteins (Atg), and regulated by intricate networks, such as mechanistic target of rapamycin (mTOR), a master regulator of autophagy, as well as mTOR-independent signaling pathways. Among mTOR-independent pathways, the transient receptor potential (TRP) calcium ion channel TRPML (mucolipin) subfamily is emerging as an important signaling channel to modulate lysosomal biogenesis and autophagy. This review discusses the recent advances in elucidating the molecular mechanisms and regulation of the autophagy process. Understanding these mechanisms may ultimately allow scientists and clinicians to control this process in order to improve human health.