UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

The WWOX gene has a WW domain containing oxidoreductase, which is located at the common fragile site FRA16D at chromosome 16q23. WWOX is a tumor suppressor gene that has been associated with several types of cancer such as hepatic, breast, lung, prostate, gastric, and ovarian. Recently WWOX has been implicated in epilepsy, where studies show homozygous loss-of-function mutation lead to early-infantile epileptic encephalopathy, spinocerebellar ataxia, intractable seizures and developmental delay, and early lethal microcephaly syndrome with epilepsy. Here we investigate two consanguineous Saudi families and we identified three probands with epileptic encephalopathy. Whole exome sequencing revealed a novel homozygous mutation in the WWOX gene in one proband. In addition, we identified a previously reported WWOX mutation in two probands. Later on these findings were confirmed with Sanger sequencing. The underlying mechanism on how WWOX mutations lead to seizure remains elusive. To date very few WWOX mutations have been associated with neurological disorder and our newly identified mutations support the notion that WWOX play an important role in neurons and will aid in better diagnosis and genetic counseling.