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. 2023 Aug 23;55(8):1573–1594. doi: 10.1038/s12276-023-01078-x

Fig. 12. Mechanism underlying parthanatos.

Fig. 12

This diagram depicts the molecular processes underlying parthanatos. ROS, ischemia, alkylating chemicals, and radiation activate PARP-1 by activating NOS, resulting in the creation of excess NO and subsequent synthesis of peroxynitrite (ONOO−). Peroxynitrite activates PARP-1, resulting in the formation of copious amounts of PAR polymer in the nucleus. Certain poly(ADP)-ribosylated carrier proteins escape from the nucleus, prompting the outer mitochondrial membrane to release apoptosis-inducing factor (AIF). AIF then enters the cytoplasm and attaches to macrophage migration inhibitory factor (MIF). AIF and MIF enter the nucleus and cause widespread DNA degradation, ultimately resulting in cell death.