Vdac1, also known as voltage-dependent anion channel 1, is a crucial regulator of mitochondrial function located in the outer mitochondrial membrane. It serves as a mitochondrial gatekeeper, regulating key cellular processes such as energy metabolism, Ca2+ homeostasis, and apoptosis. Vdac1 is involved in multiple signaling pathways, including those related to endoplasmic reticulum-mitochondria cross-talk, autophagy, and inflammation [1,2,4]. Its strategic location allows it to interact with over 100 proteins, orchestrating the integration of mitochondrial and cellular activities. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying Vdac1's functions.

In Alzheimer's disease (AD), Vdac1 is overexpressed post-mortem in the brains of patients and in amyloid precursor protein (APP) transgenic mice. Targeting Vdac1 with VBIT-4 in a 5×FAD mouse model of AD protected against mitochondrial dysfunction, mitigated brain pathology, and prevented cognitive decline, suggesting Vdac1 is a promising target for AD therapeutic intervention [2,6]. In liver fibrosis, Parkin-mediated site-specific ubiquitination of Vdac1 at lysine 53 interrupted Vdac1 oligomerization and mtDNA release, conferring protection against liver fibrosis. Knockout of Parkin aggravated the effects of a CCl4 challenge in mouse livers, indicating the importance of this Vdac1 regulation in the context of liver disease [3]. In inflammatory bowel disease, Vdac1 is overexpressed in the colon of patients and DSS-treated mice. Treatment with VBIT-12 in DSS-treated mice suppressed weight loss, diarrhea, rectal bleeding, and the inflammatory response, suggesting Vdac1-interacting molecules could be used to treat the disease [5].

In conclusion, Vdac1 is essential for maintaining mitochondrial function and regulating multiple cellular processes. Model-based research, especially using KO/CKO mouse models, has revealed its significant roles in diseases such as Alzheimer's disease, liver fibrosis, and inflammatory bowel disease. These findings provide potential therapeutic targets for treating these diseases by targeting Vdac1.