Apoptosis-inducing factor 1, mitochondrial (AIFM1) (AIFM1)

Apoptosis-inducing factor 1, mitochondrial (AIFM1) is a phylogenetically conserved flavoprotein that plays a dual role in cellular life and death [UniProt: O95831, PMID: 10490620]. In healthy cells, AIFM1 is localized within the mitochondrial intermembrane space, where it functions as an NADH oxidase essential for the proper assembly and maintenance of the mitochondrial respiratory chain complex I [UniProt: O95831, PMID: 21810461]. However, upon the induction of apoptotic signals, AIFM1 undergoes proteolytic cleavage and is released into the cytosol, subsequently translocating to the nucleus [PMID: 10490620, PMID: 11242098]. Once in the nucleus, it triggers large-scale DNA fragmentation and chromatin condensation in a caspase-independent manner, making it a key mediator of programmed cell death [PMID: 10490620, PMID: 21810461]. Due to this role, AIFM1 is a target of interest in oncology, where researchers seek to activate its pro-apoptotic pathway to eliminate resistant cancer cells [PMID: 21810461]. Conversely, in neurodegenerative diseases and ischemic injuries, AIFM1 inhibition is explored as a strategy to prevent pathological neuronal loss [PMID: 20633544]. Despite its therapeutic potential, targeting AIFM1 presents challenges because its normal mitochondrial function is vital for energy metabolism, and systemic inhibition could lead to mitochondrial dysfunction [UniProt: O95831, PMID: 11242098].

Other names

AIFPDCD8Programmed cell death protein 8Apoptosis-inducing factorApoptotic factor

Translocation from the mitochondria to the nucleus where it induces caspase-independent chromatin condensation and DNA fragmentation [PMID: 10490620, PMID: 21810461].