Incomplete autophagy: Trouble is a friend

Incomplete autophagy is an impaired self-eating process of intracellular macromolecules and organelles in which accumulated autophagosomes do not fuse with lysosomes for degradation, resulting in the blockage of autophagic flux. In this review, we summarized the literature over the past decade describing incomplete autophagy, and found that different from the double-edged sword effect of general autophagy on promoting cell survival or death, incomplete autophagy plays a crucial role in disrupting cellular homeostasis, and promotes only cell death. What matters is that incomplete autophagy is closely relevant to the pathogenesis and progression of various human diseases, which, meanwhile, intimately linking to the pharmacologic and toxicologic effects of several compounds. Here, we comprehensively reviewed the latest progress of incomplete autophagy on molecular mechanisms and signaling pathways. Moreover, implications of incomplete autophagy for pharmacotherapy are also discussed, which has great relevance for our understanding of the distinctive role of incomplete autophagy in cellular physiology and disease. Consequently, targeting incomplete autophagy may contribute to the development of novel generation therapeutic agents for diverse human diseases.