Finding the Middle Ground for Autophagic Fusion Requirements

Autophagosome/amphisome–lysosome fusion is a highly regulated process at the protein, lipid, and biochemical level. Each primary component of fusion, such as the core SNAREs, HOPS complex, or physical positioning by microtubule-associated dynein motors, are regulated at multiple points to ensure optimum conditions for autophagic flux to proceed. With the complexity of the membrane fusion system, it is not difficult to imagine how autophagic flux defect-related disorders, such as Huntington's disease, non-familial Alzheimer's disease, and Vici syndrome develop. Each membrane fusion step is regulated at the protein, lipid, and ion level. This review aims to discuss the recent developments toward understanding the regulation of autophagosome, amphisome, and lysosome fusion requirements for successful autophagic flux.