Autophagy has a complex relationship with various modes of cell death, including regulated (e.g., apoptosis, pyroptosis, and necroptosis) and catastrophic (e.g., necrosis) types of cell death. Autophagy has been implicated in association with caspase-independent cell death in apoptosis-compromised cells leading to necrosis and necroptosis. Furthermore, autophagy has been implicated as an inhibitor of both apoptosis and necrosis by preserving cellular functions, removing toxic debris, and maintaining cellular energy charge. Nevertheless, proapoptotic roles of autophagy have also been reported. Proinflammatory stimuli can activate inflammasome-dependent caspase-1 activation leading to proinflammatory cytokines maturation. Excess activation of this pathway can lead to pyroptotic cell death. Mitochondrial dysfunction plays a key role in both apoptosis signaling and the activation of the inflammasome pathway. Autophagy can influence these pathways through modulation of the mitochondrial pool. The relationships between autophagy and necroptosis or pyroptosis require further elucidation.
