更新于：2024-11-01

VDAC2

更新于：2024-11-01

基本信息

别名

hVDAC2、Outer mitochondrial membrane protein porin 2、VDAC-2

+ [3]

简介

Forms a channel through the mitochondrial outer membrane that allows diffusion of small hydrophilic molecules (By similarity). The channel adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV (By similarity). The open state has a weak anion selectivity whereas the closed state is cation-selective (By similarity). Binds various lipids, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterol cholesterol (PubMed:31015432). Binding of ceramide promotes the mitochondrial outer membrane permeabilization (MOMP) apoptotic pathway (PubMed:31015432).

关联

项与 VDAC2 相关的药物

Erastin

爱拉斯汀

靶点

SLC7A11 x VDAC1 x VDAC2 x VDAC3 x p53

作用机制

SLC7A11 modulators [+4]

在研机构

Prolexys Pharmaceuticals, Inc. [+1]

原研机构-

在研适应症

突变相关肿瘤 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

WEHI-9625

靶点

VDAC2

作用机制

VDAC2 agonists

在研机构

The Walter & Eliza Hall Institute of Medical Research

原研机构

The Walter & Eliza Hall Institute of Medical Research

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 VDAC2 相关的临床结果

登录后查看更多信息

100 项与 VDAC2 相关的转化医学

登录后查看更多信息

0 项与 VDAC2 相关的专利（医药）

登录后查看更多信息

352

项与 VDAC2 相关的文献（医药）

2025-01-01·Talanta

Metabolomics and proteomics reveal the inhibitory effect of Lactobacillus crispatus on cervical cancer

Article

作者: Qiao, Liang ; Wang, Zengyu ; Lin, Ling ; Cong, Qing ; Zhong, Lingyan ; Zheng, Jianxujie

Cervical cancer remains a significant global health issue due to its high morbidity and mortality rates. Recently, Lactobacillus crispatus has been recognized for its crucial role in maintaining cervical health. While some studies have explored the use of L. crispatus to mitigate cervical cancer, the underlying mechanisms remain largely unknown. In this study, we employed non-targeted proteomics and metabolomics to investigate how L. crispatus affects the growth of cervical cancer cells (SiHa) and normal cervical cells (Ect1/E6E7). Our findings indicated that the inhibitory effect of L. crispatus on SiHa cells was associated with various biological processes, notably the ferroptosis pathway. Specifically, L. crispatus was found to regulate the expression of proteins such as HMOX1, SLC39A14, VDAC2, ACSL4, and LPCAT3 by SiHa cells, which are closely related to ferroptosis. Additionally, it activated the tricarboxylic acid (TCA) cycle in SiHa cells, leading to increased levels of reactive oxygen species (ROS) and lipid peroxides (LPO). These results revealed the therapeutic potential of L. crispatus in targeting the ferroptosis pathway for cervical cancer treatment, opening new avenues for research and therapy in cervical cancer.

2024-10-02·Autophagy

TMX2 potentiates cell viability of hepatocellular carcinoma by promoting autophagy and mitophagy

Article

作者: Zhang, Weiyu ; Pang, Pengfei ; Ke, Haoying ; Xu, Zhijie ; Zhao, Zhiju ; Huang, Caini ; Yang, Pengfei ; Qi, Chunhui ; Qin, Haorui ; Xiao, Fei ; Chen, Yutong ; Liu, Ruiyang ; Xu, Fuyuan ; Shan, Hong ; Huang, Hongbin ; Tang, Yao

The dysregulation of membrane protein expression has been implicated in tumorigenesis and progression, including hepatocellular carcinoma (HCC). In this study, we aimed to identify membrane proteins that modulate HCC viability. To achieve this, we performed a CRISPR activation screen targeting human genes encoding membrane-associated proteins, revealing TMX2 as a potential driver of HCC cell viability. Gain- and loss-of-function experiments demonstrated that TMX2 promoted growth and tumorigenesis of HCC. Clinically, TMX2 was an independent prognostic factor for HCC patients. It was significantly upregulated in HCC tissues and associated with poor prognosis of HCC patients. Mechanistically, TMX2 was demonstrated to promote macroautophagy/autophagy by facilitating KPNB1 nuclear export and TFEB nuclear import. In addition, TMX2 interacted with VDAC2 and VADC3, assisting in the recruitment of PRKN to defective mitochondria to promote cytoprotective mitophagy during oxidative stress. Most interestingly, HCC cells responded to oxidative stress by upregulating TMX2 expression and cell autophagy. Knockdown of TMX2 enhanced the anti-tumor effect of lenvatinib. In conclusion, our findings emphasize the pivotal role of TMX2 in driving the HCC cell viability by promoting both autophagy and mitophagy. These results suggest that TMX2 May serve as a prognostic marker and promising therapeutic target for HCC treatment.Abbreviation: CCCP: Carbonyl cyanide 3-chlorophenylhydrazone; Co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeat; ER: endoplasmic reticulum; HCC: hepatocellular carcinoma; KPNB1: karyopherin subunit beta 1; PRKN: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; TFEB: transcription factor EB; TMX2: thioredoxin related transmembrane protein 2; VDAC2: voltage dependent anion channel 2; VDAC3: voltage dependent anion channel 3; WB: western blot.

2024-10-01·Ecotoxicology and Environmental Safety

Lysosomal iron accumulation and subsequent lysosomes-mitochondria iron transmission mediate PFOS-induced hepatocyte ferroptosis

Article

作者: Qiu, Tianming ; Liang, Peiyao ; Yao, Xiaofeng ; Sun, Xiance ; Yang, Guang ; Zhang, Jingyuan ; Li, Qiujuan ; Feng, Ruzhen ; Li, Jixun ; Yang, Wei

Perfluorooctane sulfonate (PFOS) is known as a persistent organic pollutant. A significant correlation between PFOS and liver ferroptosis has been unveiled, but the precise mechanism needs to be elucidated. In prior research, we found that PFOS treatment provoked mitochondrial iron overload. In this study, we observed a gradual increase in lysosomal iron in L-O2 cells after exposure to PFOS for 0.5-24 h. In PFOS-exposed L-O2 cells, suppressing autophagy relieved the lysosomal iron overload. Inhibiting transient receptor potential mucolipin 1 (TRPML1), a calcium efflux channel on the lysosomal membrane, led to a further rise in lysosomal iron levels and decreased mitochondrial iron overload during PFOS treatment. Suppressing VDAC1, a subtype of voltage-dependent anion-selective channels (VDACs) on the outer mitochondrial membrane, had no impact on PFOS-triggered mitochondrial iron overload, whereas restraining VDAC2/3 relieved this condition. Although silencing VDAC2 relieved PFOS-induced mitochondrial iron overload, it had no effect on PFOS-triggered lysosomal iron overload. Silencing VDAC3 alleviated PFOS-mediated mitochondrial iron overload and led to an additional increase in lysosomal iron. Therefore, we regarded VDAC3 as the specific VDACs subtype that mediated the lysosomes-mitochondria iron transfer. Additionally, in the presence of PFOS, an enhanced association between TRPML1 and VDAC3 was found in mice liver tissue and L-O2 cells. Our research unveils a novel regulatory mechanism of autophagy on the iron homeostasis and the effect of TRPML1-VDAC3 interaction on lysosomes-mitochondria iron transfer, giving an explanation of PFOS-induced ferroptosis and shedding some light on the role of classic calcium channels in iron transmission.