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Vacuolating Cytotoxin A Triggers Mitophagy in Helicobacter pylori-Infected Human Gastric Epithelium Cells

Helicobacter pylori (H. pylori)-derived vacuolating cytotoxin A (VacA) causes damage to various organelles, including mitochondria, and induces autophagy and cell death. However, it is unknown whether VacA-induced mitochondrial damage can develop into mitophagy. In this study, we found that H. pylor...

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Autores principales: Wang, Li, Yi, Juan, Yin, Xiao-Yang, Hou, Jin-Xia, Chen, Jing, Xie, Bei, Chen, Gang, Wang, Qun-Feng, Wang, Li-Na, Wang, Xiao-Yuan, Sun, Jing, Huo, Lei-Ming, Che, Tuan-Jie, Wei, Hu-Lai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329568/
https://www.ncbi.nlm.nih.gov/pubmed/35912184
http://dx.doi.org/10.3389/fonc.2022.881829
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author Wang, Li
Yi, Juan
Yin, Xiao-Yang
Hou, Jin-Xia
Chen, Jing
Xie, Bei
Chen, Gang
Wang, Qun-Feng
Wang, Li-Na
Wang, Xiao-Yuan
Sun, Jing
Huo, Lei-Ming
Che, Tuan-Jie
Wei, Hu-Lai
author_facet Wang, Li
Yi, Juan
Yin, Xiao-Yang
Hou, Jin-Xia
Chen, Jing
Xie, Bei
Chen, Gang
Wang, Qun-Feng
Wang, Li-Na
Wang, Xiao-Yuan
Sun, Jing
Huo, Lei-Ming
Che, Tuan-Jie
Wei, Hu-Lai
author_sort Wang, Li
collection PubMed
description Helicobacter pylori (H. pylori)-derived vacuolating cytotoxin A (VacA) causes damage to various organelles, including mitochondria, and induces autophagy and cell death. However, it is unknown whether VacA-induced mitochondrial damage can develop into mitophagy. In this study, we found that H. pylori, H. pylori culture filtrate (HPCF), and VacA could activate autophagy in a gastric epithelial cell line (GES-1). VacA-caused mitochondrial depolarization retards the import of PINK1 into the damaged mitochondria and evokes mitophagy. And, among mass spectrometry (LC-MS/MS) identified 25 mitochondrial proteins bound with VacA, Tom20, Tom40, and Tom70, TOM complexes responsible for PINK1 import, were further identified as having the ability to bind VacA in vitro using pull-down assay, co-immunoprecipitation, and protein–protein docking. Additionally, we found that the cell membrane protein STOM and the mitochondrial inner membrane protein PGAM5 also interacted with VacA. These findings suggest that VacA captured by STOM forms endosomes to enter cells and target mitochondria. Then, VacA is transported into the mitochondrial membrane space through the TOM complexes, and PGAM5 aids in inserting VacA into the inner mitochondrial membrane to destroy the membrane potential, which promotes PINK1 accumulation and Parkin recruitment to induce mitophagy. This study helps us understand VacA entering mitochondria to induce the mitophagy process.
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spelling pubmed-93295682022-07-29 Vacuolating Cytotoxin A Triggers Mitophagy in Helicobacter pylori-Infected Human Gastric Epithelium Cells Wang, Li Yi, Juan Yin, Xiao-Yang Hou, Jin-Xia Chen, Jing Xie, Bei Chen, Gang Wang, Qun-Feng Wang, Li-Na Wang, Xiao-Yuan Sun, Jing Huo, Lei-Ming Che, Tuan-Jie Wei, Hu-Lai Front Oncol Oncology Helicobacter pylori (H. pylori)-derived vacuolating cytotoxin A (VacA) causes damage to various organelles, including mitochondria, and induces autophagy and cell death. However, it is unknown whether VacA-induced mitochondrial damage can develop into mitophagy. In this study, we found that H. pylori, H. pylori culture filtrate (HPCF), and VacA could activate autophagy in a gastric epithelial cell line (GES-1). VacA-caused mitochondrial depolarization retards the import of PINK1 into the damaged mitochondria and evokes mitophagy. And, among mass spectrometry (LC-MS/MS) identified 25 mitochondrial proteins bound with VacA, Tom20, Tom40, and Tom70, TOM complexes responsible for PINK1 import, were further identified as having the ability to bind VacA in vitro using pull-down assay, co-immunoprecipitation, and protein–protein docking. Additionally, we found that the cell membrane protein STOM and the mitochondrial inner membrane protein PGAM5 also interacted with VacA. These findings suggest that VacA captured by STOM forms endosomes to enter cells and target mitochondria. Then, VacA is transported into the mitochondrial membrane space through the TOM complexes, and PGAM5 aids in inserting VacA into the inner mitochondrial membrane to destroy the membrane potential, which promotes PINK1 accumulation and Parkin recruitment to induce mitophagy. This study helps us understand VacA entering mitochondria to induce the mitophagy process. Frontiers Media S.A. 2022-07-14 /pmc/articles/PMC9329568/ /pubmed/35912184 http://dx.doi.org/10.3389/fonc.2022.881829 Text en Copyright © 2022 Wang, Yi, Yin, Hou, Chen, Xie, Chen, Wang, Wang, Wang, Sun, Huo, Che and Wei https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Wang, Li
Yi, Juan
Yin, Xiao-Yang
Hou, Jin-Xia
Chen, Jing
Xie, Bei
Chen, Gang
Wang, Qun-Feng
Wang, Li-Na
Wang, Xiao-Yuan
Sun, Jing
Huo, Lei-Ming
Che, Tuan-Jie
Wei, Hu-Lai
Vacuolating Cytotoxin A Triggers Mitophagy in Helicobacter pylori-Infected Human Gastric Epithelium Cells
title Vacuolating Cytotoxin A Triggers Mitophagy in Helicobacter pylori-Infected Human Gastric Epithelium Cells
title_full Vacuolating Cytotoxin A Triggers Mitophagy in Helicobacter pylori-Infected Human Gastric Epithelium Cells
title_fullStr Vacuolating Cytotoxin A Triggers Mitophagy in Helicobacter pylori-Infected Human Gastric Epithelium Cells
title_full_unstemmed Vacuolating Cytotoxin A Triggers Mitophagy in Helicobacter pylori-Infected Human Gastric Epithelium Cells
title_short Vacuolating Cytotoxin A Triggers Mitophagy in Helicobacter pylori-Infected Human Gastric Epithelium Cells
title_sort vacuolating cytotoxin a triggers mitophagy in helicobacter pylori-infected human gastric epithelium cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329568/
https://www.ncbi.nlm.nih.gov/pubmed/35912184
http://dx.doi.org/10.3389/fonc.2022.881829
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