Shiga toxin 2 A-subunit induces mitochondrial damage, mitophagy and apoptosis via the interaction of Tom20 in Caco-2 cells

作者：Jie Tang, Xiaoxue Lu, Tao Zhang, Yuyang Feng, Qiaolin Xu, Jing Li, Yuanzhi Lan, Hua-xing Luo, Linghai Zeng, Yuanyuan Xiang, Yan Zhang, Qian Li, Xuhu Mao, Bin Tang, Dongzhu Zeng · 发表于：Heliyon · 年份：2023 · DOI：10.1016/j.heliyon.2023.e20012 · 被引用次数：6 · 研究领域：Escherichia coli research studies、Cytomegalovirus and herpesvirus research、Prion Diseases and Protein Misfolding

(STEC), which causes epidemic outbreaks of gastrointestinal sickness and potentially fatal sequela hemolytic uremic syndrome (HUS). Most studies on Stx2-induced apoptosis have been performed with holotoxins, but the mechanism of how the A and B subunits of Stx2 cause apoptosis in cells is not clear. Here, we found that Stx2 A-subunit (Stx2A) induced mitochondrial damage, PINK1/Parkin-dependent mitophagy and apoptosis in Caco-2 cells. PINK1/Parkin-dependent mitophagy caused by Stx2A reduced apoptosis by decreasing the accumulation of reactive oxidative species (ROS). Mechanistically, Stx2A interacts with Tom20 on mitochondria to initiate the translocation of Bax to mitochondria, leading to mitochondrial damage and apoptosis. Overall, these data suggested that Stx2A induces mitochondrial damage, mitophagy and apoptosis via the interaction of Tom20 in Caco-2 cells and that mitophagy caused by Stx2A ameliorates apoptosis by eliminating damaged mitochondria. These findings provide evidence for the potential use of Tom20 inhibition as an anti-Shiga toxin therapy.