Mitochondrial voltage-dependent anion channel is responsible for paraquat cytotoxicity.

百草枯是一种除草剂，可形成活性氧代谢物，对人体有毒。在细胞毒性机制方面，我们发现线粒体上有一个NADH-醌氧化还原酶活性，并提出电压依赖性阴离子通道VDAC参与。当离体大鼠线粒体与NADH和百草枯共同孵育时，线粒体外膜的NADH-醌氧化还原酶活性产生H_2O_2，线粒体受到损伤。苯醌、4，4 '-二异硫氰酸二苯乙烯-2，29-二硫酸和抗VDAC 1抗体可抑制上述变化。酶谱分析表明，在聚丙烯酰胺凝胶电泳中，该酶活性位于500 kDa处，Western blot显示该酶含有VDAC蛋白。过表达VDAC 1的HeLa细胞经百草枯处理后，细胞内H_2O_2产生量增加，对百草枯更敏感。而VDAC 1基因敲除细胞的线粒体不产生H_2O_2，且在百草枯处理后有较高的存活率。结果表明，线粒体VDAC蛋白与介导百草枯毒性的活性氧有关。

Paraquat is an herbicide that forms reactive oxygen metabolites, which are toxic to humans. With respect to the cytotoxicmechanisms, we identified a NADH-quinone oxidoreductasem activity located on the mitochondria and propose the participationof a voltage-dependent anion channel, VDAC.When isolated rat mitochondria were incubated with NADH and paraquat, H_2O_2 was produced by NADH-quinoneoxidoreductasem activity of the outer membrane and the mitochondria were damaged. These changes were suppressed bybenzoquinone, 4,4'-diisothiocyanatostilbene-2,29-disulfic acid and anti-VDAC1 antibody. NADH-quinone oxidoreductasemactivity was located by zymography at the 500kDa band on native-polyacrylamide electrophoresis, and it contained VDAC protein in a Western blot. VDAC1-overexpressed HeLa cells treated with paraquat produced more intracellular H_2O_2 thancontrols and were more sensitive to paraquat. In contrast, mitochondria in VDAC1 knockdown cells did not produce H_2O_2 andhad a higher survival rate after exposure to paraquat. The results indicate that mitochondrial VDAC protein was associated with reactive oxygen species that mediated paraquat toxicity.