Figure 2: Schematic representation of the AIF translocation from the mitochondria to the nucleus upon apoptotic stimuli and its regulation by other proteins. Calpains will cleave AIF from the IMM. BCL-2 pro-apoptotic protein BID, among others, will promote the MOMP and pore formation. PAR polymers (produced by the overactivation of PARP-1) and CHCHD4 protein are also involved in the translocation of AIF from the mitochondria. Once in the cytosol, AIF will bind to CypA. The HSP70 chaperone can neutralize AIF in the cytosol. In the nucleus, the AIF/CypA complex will cooperate with H2AX to induce chromatin condensation and large-scale DNA fragmentation. AIF: Apoptosis-inducing factor; ATP: adenosine triphosphate; BAK: BCL-2 homologous antagonist killer; BAX: BCL-2-associated X; BID: BH3 interacting-domain death agonist; CHCHD4: coiled-coil-helix-coiled-coil-helix domain-containing protein 4; CypA: cyclophilin A; H2AX: H2A histone family member X; HSP70: heat shock protein 70; PAR: poly-ADP ribose; PARP-1: poly (ADP–ribose) polymerase 1.