Apoptosis-inducing factor 1, mitochondrial and Endonuclease G (AIF and EndoG)

Apoptosis-inducing factor (AIF, specifically AIFM1) and Endonuclease G (EndoG) are mitochondrial proteins that serve as key mediators of caspase-independent cell death. Under normal physiological conditions, AIF functions as a flavin adenine dinucleotide (FAD)-dependent NADH oxidoreductase essential for mitochondrial respiratory chain assembly, while EndoG is involved in mitochondrial DNA maintenance and repair. Following cellular injury or pro-apoptotic signaling, these proteins are released from the mitochondrial intermembrane space and translocate to the nucleus. Once in the nucleus, AIF promotes chromatin condensation and recruits nucleases, while EndoG directly catalyzes DNA fragmentation, leading to a form of programmed cell death known as parthanatos or caspase-independent apoptosis. This pathway is critically involved in the pathogenesis of neurodegenerative diseases, stroke, and myocardial infarction, where excessive cell death occurs. Consequently, inhibitors of AIF translocation or PARP-1 (which triggers AIF release) are being investigated for neuroprotection, while the induction of this pathway is a potential strategy for treating apoptosis-resistant cancers.

Other names

AIFM1PDCD8ENDOGApoptosis-inducing factorEndoGMitochondrial nuclease

Inhibition of mitochondrial release, nuclear translocation, or DNA binding of AIF and EndoG; or indirect modulation of the pathway via PARP-1 inhibition to prevent PAR-mediated AIF release.