Fig. 1

Mitochondrial dysfunction in ETC dysfunction, production of mtROS, cell apoptosis and pyroptosis, inflammatory response. a When oxygen and glucose levels are low, the normal ion gradients cannot be maintained, mitochondrial oxidative phosphorylation is impaired, ATP synthesis is reduced, ATP-dependent ion transporters such as sodium pumps and calcium pumps are disabled, and Ca²⁺ excretion is blocked, leading to calcium overload and excessive extracellular glutamate levels. Moreover, owing to dysfunction of the sodium and potassium pumps, mitochondria cannot function properly. b When ROS levels exceed their scavenging capacity, downstream effectors generated by excess ROS are triggered, resulting in different degrees of OS, especially mtROS generation. With the opening of the mitochondrial mPTP and the disturbance of ion channels, the release of mtROS is further induced. The high level of mtROS continues to activate mPTP opening through positive feedback, further aggravating mitochondrial damage. c Elevated levels of mtROS trigger cellular stress, disrupting mitochondrial homeostasis. The proapoptotic proteins BAX and BAK binds each other after activation, leading to MOMP. This results in the formation of numerous small pores in the mitochondrial membrane, releasing the pro-apoptotic factor CytC or mtDNA into the cytoplasm. CytC binds to Apaf1, forming “apoptotic bodies” that activate caspase-9 and initiate a cascade of events. MtDNA is recognized by cGAS, which activates STING to induce an inflammatory response. d cGAS-STING signaling triggers an inflammatory response, which subsequently induces inflammasome and pyroptosis