Fig. 4

The role of mitochondrial ROS in the regulation of the autophagy/inflammasome axis at MAMs in non-malignant cells, cancer cells, and chemosensitized cells. MAMs are signaling hubs, playing crucial roles in the crosstalk between autophagy and inflammasome activation, as well as intracellular Ca²⁺ signaling, mitochondrial lipid metabolism, and bioenergetics. Mitochondrial dysfunction and subsequent mitochondrial ROS generation activate autophagy/mitophagy, which negatively regulates NLRP3 inflammasome activation in non-malignant cells. Cancer cells are characterized by elevated mitochondrial ROS levels, accompanied by the upregulation of antioxidant machinery components. The role of mitochondrial ROS in the crosstalk between autophagy and inflammasome activation in cancer cells remains unclear. In chemosensitized cells, excessive production of mitochondrial ROS results in autophagic and pyroptotic cell death. Although the role of IP3R in the regulation of the autophagy/inflammasome axis remains unknown, IP3R inhibition can suppress tumor growth