1.B.8.1.3
VDAC1, VDAC-1 or VDAC porin of 283 aas, which is > 99% identical to human (P21796) and mouse (60932) VDAC1. Mammals possess three VDACs (VDAC1, 2 and 3) encoded by three genes, but they are all similar in sequence (~60-70% identical) (Messina et al., 2011).  The 3-d structure of the human VDAC1 is known (PDB ID 2JK4; Bayrhuber et al. 2008).  Reviewed by Shoshan-Barmatz et al. 2015.  VDAC1 is found both in mitochondria and the plasma membrane (Lawen et al. 2005) where it may cause cytoplasmic ATP loss.. It may be involved in cancer (Shoshan-Barmatz et al. 2017) and Alzheimer's disease (AD) (Shoshan-Barmatz et al. 2018). Along with its low toxicity profile and high antioxidant activity, the gallic acid derivative, AntiOxBEN3, strongly inhibits calcium-dependent mitochondrial permeability transition pore (mPTP) opening (Teixeira et al. 2018). VDAC dimerization plays a role in mitochondrial metabolic regulation and apoptosis in response to cytosolic acidification during cellular stress, and E73 is involved (Bergdoll et al. 2018). Inhibiting VDAC1 overproduction and plasma membrane insertion in β-cells preserves insulin secretion in diabetes (Zhang et al. 2018). βII and βIII-tubulin, bound to VDAC, regulate VDAC permeability (Puurand et al. 2019). This VDAC porin interacts with carrier precursors arriving in the intermembrane space and recruits TIM22 complexes, thus ensuring efficient transfer of the precursors to the inner membrane translocase (Ellenrieder et al. 2019). A method has been develped to determine the number of VDAC1 channels (and other integral membrane proteins) in nanodiscs under various assembly conditions (Häusler et al. 2020). Stable low-conducting states of human VDAC1 predominantly take place from disordered events and do not result from the displacement of a voltage sensor or a significant change in the pore. Conductance jumps reveal entropy as a key factor for VDAC gating (Preto et al. 2022). The lysyl residue at position 12 in the pore interior is responsible for most of VDAC's voltage sensitivity (Ngo et al. 2022).  Oral administration of VDAC1-derived small peptides increases circulating testosterone levels in male rats (Martinez-Arguelles et al. 2022). Possible alternative conformational states of VDAC have been considered for the closed state (Mannella 2023). HSP90 C-terminal domain inhibition promotes VDAC1 oligomerization via decreasing K274 mono-ubiquitination in hepatocellular carcinoma (Zhang et al. 2023). Silencing the mitochondrial gatekeeper, VDAC1, is a potential treatment for bladder cancer (Alhozeel et al. 2024). TRO19622 at 5 μM and 50 μM is an inhibitor of VDACs (Garriga et al. 2024).  VDAC1 oligomerization inhibitors increase pigmentation in zebrafish and in human skin explants (Lv et al. 2024). VDAC1-based peptides are potential modulators of VDAC1 interactions with its partners and as a therapeutic for cancer, NASH, and diabetes (Shteinfer-Kuzmine et al. 2024).  VDAC1 is an important negative regulator of melanogenesis (Wang et al. 2022). Knockdown of human VDAC1 promotes ferroptosis in diffuse large B-cell lymphoma (Lin et al. 2025).  The human ortholog is almost identical. VDAC1 is a mitochondria-related target of Duchenne muscular dystrophy (Wu et al. 2025).  Resveratrol's pro-apoptotic effects in cancer are mediated through the interaction and oligomerization of the  mitochondrial VDAC1 (Raviv et al. 2025).  A comprehensive analysis of VDAC1 in gynecological tumors as well as a structure-based virtual screening of its natural inhibitorshave been reported (Li et al. 2025).