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. Author manuscript; available in PMC: 2015 Jun 3.
Published in final edited form as: Ann N Y Acad Sci. 2008 Dec;1147:233–241. doi: 10.1196/annals.1427.014

Figure 2.

Figure 2

PARP-1 activation and role of PAR in Parthanatos. DNA damage in cell stress conditions leads to PARP-1 activation. Active PARP-1 uses NAD+ as a substrate and builds PAR on itself (auto-modification) and on various acceptor proteins (hetero-modification) in the nucleus. PARG can hydrolyze PAR in the nucleus to generate fee PAR or ADP-ribose. PAR accumulation induces cell death. PAR is mainly generated in the nucleus and translocates to cytosol either as attached polymer to poly(ADP-ribosyl)ated proteins or as a free polymer. Cytosolic isoforms of PARG can degrade PAR when present in optimal amounts in relation to PAR generated. In the cytosol PAR interacts with mitochondria to induce AIF release. On translocation to nucleus, AIF binds to DNA and mediates a large scale DNA fragmentation and cell death.