Bok, also known as Bcl-2-related ovarian killer, is a member of the BCL-2 family. Initially labeled as "pro-apoptotic" due to cell death caused by its over-expression, it has become clear that its functions are more complex. Bok is widely expressed in tissues beyond ovaries. It plays roles in regulating endoplasmic reticulum/mitochondria contact sites, mitochondrial dynamics, and is involved in the regulation of the intrinsic apoptotic pathway, although its exact apoptotic mechanism is controversial [1,3,4].

In Alzheimer's disease, neuron-specific loss of Bok in patients and APPswe/PS1dE9 mice is associated with mitochondrial damage and mitophagy defects. Bok is the key to Parkin-mediated mitophagy through competitive binding to the MCL1/Parkin complex. Overexpressing bok in hippocampal neurons of APP/PS1 mice alleviates mitophagy and mitochondrial malfunction, improving cognitive function, while knockdown worsens Alzheimer's-related changes [2]. In murine embryonic fibroblasts, deletion of Bok expression by Nuclease technology-mediated gene editing reduces mitochondrial fusion rate, leading to mitochondrial fragmentation, but does not alter calcium mobilization via IP3Rs or calcium influx into the mitochondria. Bok deletion also enhances mitochondrial spare respiratory capacity and membrane potential, and does not play a major role in apoptotic signaling [5].

In conclusion, Bok has diverse functions, including in mitochondrial fusion, morphology, and mitophagy. Gene-knockout models in mice have revealed its significance in Alzheimer's disease, highlighting its potential as a therapeutic target. Its role in maintaining mitochondrial and cellular homeostasis is crucial, and further study of Bok using these models may provide more insights into disease mechanisms and treatment strategies.