Figure 2. MIF is the executor for PARP-1 dependent cell death (parthanatos).

Stresses induce DNA damage, PARP1 activation, and subsequently PAR formation. PAR facilitates the release of AIF from mitochondria. AIF recruits MIF to the nucleus, where MIF cleaves genomic DNA into large DNA fragments and causes cell death. Interference with this cascade by blocking either the formation of the AIF-MIF complex or MIF nuclease activity prevents DNA fragmentation and promotes cell survival.