Vdac2, or voltage-dependent anion channel 2, is a key protein in the VDAC family. It contributes to oxidative metabolism by facilitating solute transport across the outer mitochondrial membrane [7]. It is also involved in mediating local Ca(2+) transport from the sarcoplasmic reticulum to mitochondria, especially in cardiomyocytes [7]. Additionally, Vdac2 has a role in the regulation of apoptosis, interacting with the BCL-2 protein family [3].

In cancer, Vdac2 has been studied in multiple contexts. Nedd4-mediated ubiquitination of VDAC2/3 suppresses erastin-induced ferroptosis in melanoma, with Nedd4 depletion increasing cancer cell sensitivity to erastin [1]. In renal cell carcinoma (RCC), STING binds to VDAC2, and STING depletion affects mitochondrial function and RCC growth [4]. In hepatocellular carcinoma, celastrol directly targets VDAC2 to induce mitochondria-dependent cell death [5]. In lung adenocarcinoma, Hedyotis diffusa injection induces ferroptosis via the Bax/Bcl2/VDAC2/3 axis [6]. In nasopharyngeal carcinoma, TRIM21 promotes VDAC2 degradation via K48-linked ubiquitination, inhibiting mitochondrial DNA release and type-I interferon responses after radiation [8]. In sepsis-induced myocardial dysfunction, VDAC2 malonylation is involved in mitochondrial-related ferroptosis [2].

In conclusion, Vdac2 has diverse functions in metabolism, apoptosis, and Ca(2+) transport. Its role in multiple diseases, especially cancer, has been illuminated through various studies. Understanding Vdac2's functions can potentially provide new therapeutic strategies for treating cancer, sepsis-induced myocardial dysfunction, and other related diseases.