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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9329568 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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