The inducible role of autophagy in cell death: emerging evidence and future perspectives.

Abstract

Background: Autophagy is a lysosome-dependent degradation pathway for recycling intracellular materials and removing damaged organelles, and it is usually considered a prosurvival process in response to stress stimuli. However, increasing evidence suggests that autophagy can also drive cell death in a context-dependent manner. The bulk degradation of cell contents and the accumulation of autophagosomes are recognized as the mechanisms of cell death induced by autophagy alone. However, autophagy can also drive other forms of regulated cell death (RCD) whose mechanisms are not related to excessive autophagic vacuolization. Notably, few reviews address studies on the transformation from autophagy to RCD, and the underlying molecular mechanisms are still vague.

Aim of review: This review aims to summarize the existing studies on autophagy-mediated RCD, to elucidate the mechanism by which autophagy initiates RCD, and to comprehensively understand the role of autophagy in determining cell fate.

Key scientific concepts of review: This review highlights the prodeath effect of autophagy, which is distinct from the generally perceived cytoprotective role, and its mechanisms are mainly associated with the selective degradation of proteins or organelles essential for cell survival and the direct involvement of the autophagy machinery in cell death. Additionally, this review highlights the need for better manipulation of autophagy activation or inhibition in different pathological contexts, depending on clinical purpose.