Figure 3.

PKM2 mediates proinflammatory non-apoptotic-regulated cell death. PKM2 mediates proinflammatory non-apoptotic-regulated cell death such as pyroptosis and ferroptosis. The specific mechanisms by which PKM2 regulates pyroptosis and ferroptosis remain unknown, however, a considerable number of studies imply a potential connection between PKM2 and these non-apoptotic-regulated cell death. PKM2-dependent glycolysis promotes EIF2AK2 phosphorylation and inflammasome activation, while the activation of inflammasome also activates Caspase-1 and thus leading to pyroptosis. Moreover, PKM2-mediated Warburg effect can induce ferroptosis. The glucose metabolism dysfunction caused by PKM2 mediates the reducibility function of GSH, leading to ferroptosis. Thus, targeting PKM2 is a potential approach of regulating proinflammatory non-apoptotic-regulated cell death.