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. Author manuscript; available in PMC: 2010 Aug 1.
Published in final edited form as: Exp Neurol. 2009 Mar 28;218(2):193–202. doi: 10.1016/j.expneurol.2009.03.020

Figure 3. Schematic model of PARP-1-, PAR polymer- and AIF-mediated death signal in parthanatos.

Figure 3

PARP-1 activation, PAR polymer formation, mitochondrial AIF release, AIF-mediated chromatin condensation and DNA fragmentation are four key steps in parthanatos. Step 1, DNA damage by NMDA or MNNG administration activates PARP-1. Excitotoxic activation of NMDA receptor can induce calcium influx, nNOS activation, NO production and reactive oxygen species generation. The reaction between NO and superoxide anion generates the potent oxidant preoxynitrite, which leads to DNA damage. Other agents like MNNG, free radicals, hydrogen peroxide, hydroxyl radical or ionizing radiation cause DNA damage, which activate PARP-1. Step 2, PARP-1 activation catalyzes PAR polymer formation, which translocates from the nucleus to the mitochondria. Step 3, PAR polymer mediates AIF release from mitochondria and translocation to nucleus. Step 4, AIF causes chromatin condensation and large DNA fragmentation through an unknown mechanism.