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

作者全名："Tang, Jie; Lu, Xiaoxue; Zhang, Tao; Feng, Yuyang; Xu, Qiaolin; Li, Jing; Lan, Yuanzhi; Luo, Huaxing; Zeng, Linghai; Xiang, Yuanyuan; Zhang, Yan; Li, Qian; Mao, Xuhu; Tang, Bin; Zeng, Dongzhu"

作者地址："[Tang, Jie; Zhang, Tao; Xu, Qiaolin; Li, Jing; Lan, Yuanzhi; Luo, Huaxing; Zeng, Linghai; Xiang, Yuanyuan; Zhang, Yan; Zeng, Dongzhu] Chongqing Med Univ, Dept Gen Surg, Affiliated Hosp 3, Chongqing 401120, Peoples R China; [Lu, Xiaoxue; Feng, Yuyang; Li, Qian; Mao, Xuhu] Army Med Univ, Mil Med Univ 3, Dept Clin Microbiol & Immunol, Coll Pharm & Med Lab, Chongqing, Peoples R China; [Tang, Bin] Chongqing Univ, Chongqing Univ Jiangjin Hosp, Sch Med, Dept Clin Lab, Chongqing 402260, Peoples R China"

通信作者："Zeng, DZ (通讯作者)，Chongqing Med Univ, Dept Gen Surg, Affiliated Hosp 3, Chongqing 401120, Peoples R China.; Tang, B (通讯作者)，Chongqing Univ, Chongqing Univ Jiangjin Hosp, Sch Med, Dept Clin Lab, Chongqing 402260, Peoples R China."

来源：HELIYON

ESI学科分类：　

WOS号：WOS:001133497300001

JCR分区：Q1

影响因子：3.4

年份：2023

卷号：9

期号：9

开始页：　

结束页：　

文献类型：Article

关键词：Shiga toxin; Shiga toxin type 2; Mitophagy; Apoptosis; Tom20

摘要："Shiga toxin type 2 (Stx2) is the primary virulence factor produced by Shiga toxin-producing enterohemorrhagic Escherichia coli (STEC), which causes epidemic outbreaks of gastrointestinal sickness and potentially fatal sequela hemolytic uremic syndrome (HUS). Most studies on Stx2induced 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."

基金机构："Natural Science Foundation of Chongqing [cstc2020jcyjmsxmX0220]; Scientific Research Incubation Project, The Third Affiliated Hospital of Chongqing Medical University [KY20079]"

基金资助正文："This work was supported by grants from the Natural Science Foundation of Chongqing (no. cstc2020jcyjmsxmX0220) and the Scientific Research Incubation Project, The Third Affiliated Hospital of Chongqing Medical University (no. KY20079) ."