Apoptosis-inducing factor: a mitochondrial protein associated with metabolic diseases—a narrative review

BACKGROUND AND OBJECTIVE: Apoptosis-inducing factor (AIF), a flavin protein in mitochondria, is originally found to induce apoptosis under the stimulation of pro-apoptotic factors. As a mitochondrial flavin adenine dinucleotide-dependent oxidoreductase, AIF is involved in the regulation of mammalian cell metabolism by regulating respiratory enzyme activity, antioxidant stress, promoting mitochondrial autophagy and glucose uptake, etc. Herein, we focused on the research progress regarding the molecular mechanism of AIF in metabolic mediation and the recent research on AIF in metabolic diseases, as well as the AIF-mediated apoptotic process. METHODS: Articles for this paper were obtained by reviewing the literature related to the role of AIF in metabolic diseases on PubMed. The search terms included the following: “apoptosis”, “metabolism” or “metabolic diseases” plus “apoptosis-inducing factor”. The titles, abstracts, and full texts of relevant English-language publications published from October 1996 to June 2022 were manually screened to clarify the role of AIF in metabolic diseases. KEY CONTENT AND FINDINGS: We found that AIF played an important role in a variety of metabolically-related diseases, such as diabetes, obesity, metabolic syndrome, and tumor metabolism, by mediating apoptosis. CONCLUSIONS: We summarized the important role of AIF in a variety of metabolic diseases, which might help to further expand the understanding of AIF and to develop AIF-related therapeutic targets.