Figure 1: Schematic representation of the different human AIF isoforms and their binding domains. Shown are the exons of the AIF gene (E1–E16) and the N-terminal, MLS, TMD, FAD, NLS, NADH and C-terminal domains, together with the HSP70, DNA, MIF and CypA biding sites of the different AIF protein forms. Mitochondrial-processing peptidase and calpains cleavage sites are also revealed, generating the mature AIF and the pro-apoptotic AIF forms, respectively. The difference in the color intensity of the TMD domain of AIF2 reflects the alternative usage of exon 2b, affecting the TMD segment. AIFsh, AIFsh2, and AIFsh3 are generated by the alternative splicing of exon 9b. AIFsh3 has a structure similar to AIFsh2 but with the deletion of exon 2, which leads to the loss of MLS and TMD domains. AIF: Apoptosis-inducing factor; CypA: cyclophilin A; FAD: flavin adenine dinucleotide; HSP70: heat shock protein 70; MIF: migration inhibitory factor; MLS: mitochondrial localization sequence; MPP: mitochondrial-processing peptidase; NADH: nicotinamide adenine dinucleotide; NLS: nuclear localization sequences; TMD: transmembrane domain.