Porphyromonas gingivalis hijacks mitophagy and lysosomal function to persist in endothelial cells
IntroductionThe direct infection of endothelial cells by Porphyromonas gingivalis (P. gingivalis), a keystone periodontal pathogen, has been implicated in the development of atherosclerosis. While non-selective autophagy facilitates its intracellular persistence in endothelial cells, the role of sel...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| author | Cheng Zheng Jianmin Huang Shengming Xu Bin Lu Hanxin Que Tianhao Chen Yubo Hou Yubo Hou Linlin He Linlin He Xia Fan Fa-Ming Chen Yi Wang Yi Wang Hui Deng Hui Deng |
| author_facet | Cheng Zheng Jianmin Huang Shengming Xu Bin Lu Hanxin Que Tianhao Chen Yubo Hou Yubo Hou Linlin He Linlin He Xia Fan Fa-Ming Chen Yi Wang Yi Wang Hui Deng Hui Deng |
| author_sort | Cheng Zheng |
| collection | DOAJ |
| description | IntroductionThe direct infection of endothelial cells by Porphyromonas gingivalis (P. gingivalis), a keystone periodontal pathogen, has been implicated in the development of atherosclerosis. While non-selective autophagy facilitates its intracellular persistence in endothelial cells, the role of selective autophagy in this process remains unclear. This study investigated whether P. gingivalis hijacks mitophagy and lysosomes to persist in endothelial cells.MethodsHuman aortic endothelial cells (HAECs) were infected with P. gingivalis for 24 h. Mitophagy was detected by Western Blotting (WB), immunofluorescence, and transmission electron microscopy. Lysosomal function was assessed by acridine orange staining, lysosensor staining, and WB. The effects of mitophagy and lysosomes on P. gingivalis intracellular survival were evaluated by antibiotic protection assays and SYTO-9 staining.ResultsOur data demonstrated that P. gingivalis initiates PTENinduced putative kinase 1 (PINK1)-Parkin-mediated mitophagy in HAECs, leading to increased formation of autophagosomes and mitophagosomes, but disrupted autophagy/mitophagy flux. This blockage of autophagy/mitophagy flux was linked to lysosomal dysfunction, characterized by increased lysosome number, lysosomal membrane permeabilization, disruption of the lysosomal acidic environment, and decreased enzymatic activity. Additionally, antibiotic protection assays and SYTO-9 staining further revealed that P. gingivalis promotes its intracellular survival in endothelial cells by initiating mitophagy and impairing lysosomal function. Furthermore, the mitophagy activator decreased the co-localization of P. gingivalis with microtubule-associated protein 1 light chain 3 (LC3)-p62, LC3-NDP52, and lysosomal-associated membrane protein 1 (LAMP1), suggesting that P. gingivalis-initiated mitophagy inhibited xenophagosome formation and autophagosome/xenophagosome-lysosome fusion.ConclusionOur findings reveal that P. gingivalis may promote its intracellular survival in endothelial cells by initiating PINK1-Parkin-mediated mitophagy and impairing lysosomal function, thereby suppressing xenophagosome formation and xenophagic degradation. This study provides new insights into the mechanisms by which P. gingivalis persists in endothelial cells and its potential role in atherosclerosis progression. |
| format | Article |
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| publishDate | 2025-08-01 |
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| spelling | doaj-art-cac9d9515a8b4be388cc2383bc77f9212025-08-20T03:40:50ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-08-011510.3389/fcimb.2025.16133661613366Porphyromonas gingivalis hijacks mitophagy and lysosomal function to persist in endothelial cellsCheng Zheng0Jianmin Huang1Shengming Xu2Bin Lu3Hanxin Que4Tianhao Chen5Yubo Hou6Yubo Hou7Linlin He8Linlin He9Xia Fan10Fa-Ming Chen11Yi Wang12Yi Wang13Hui Deng14Hui Deng15Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Periodontology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Periodontology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi’ an, Shanxi, ChinaInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Orthodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Periodontology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaIntroductionThe direct infection of endothelial cells by Porphyromonas gingivalis (P. gingivalis), a keystone periodontal pathogen, has been implicated in the development of atherosclerosis. While non-selective autophagy facilitates its intracellular persistence in endothelial cells, the role of selective autophagy in this process remains unclear. This study investigated whether P. gingivalis hijacks mitophagy and lysosomes to persist in endothelial cells.MethodsHuman aortic endothelial cells (HAECs) were infected with P. gingivalis for 24 h. Mitophagy was detected by Western Blotting (WB), immunofluorescence, and transmission electron microscopy. Lysosomal function was assessed by acridine orange staining, lysosensor staining, and WB. The effects of mitophagy and lysosomes on P. gingivalis intracellular survival were evaluated by antibiotic protection assays and SYTO-9 staining.ResultsOur data demonstrated that P. gingivalis initiates PTENinduced putative kinase 1 (PINK1)-Parkin-mediated mitophagy in HAECs, leading to increased formation of autophagosomes and mitophagosomes, but disrupted autophagy/mitophagy flux. This blockage of autophagy/mitophagy flux was linked to lysosomal dysfunction, characterized by increased lysosome number, lysosomal membrane permeabilization, disruption of the lysosomal acidic environment, and decreased enzymatic activity. Additionally, antibiotic protection assays and SYTO-9 staining further revealed that P. gingivalis promotes its intracellular survival in endothelial cells by initiating mitophagy and impairing lysosomal function. Furthermore, the mitophagy activator decreased the co-localization of P. gingivalis with microtubule-associated protein 1 light chain 3 (LC3)-p62, LC3-NDP52, and lysosomal-associated membrane protein 1 (LAMP1), suggesting that P. gingivalis-initiated mitophagy inhibited xenophagosome formation and autophagosome/xenophagosome-lysosome fusion.ConclusionOur findings reveal that P. gingivalis may promote its intracellular survival in endothelial cells by initiating PINK1-Parkin-mediated mitophagy and impairing lysosomal function, thereby suppressing xenophagosome formation and xenophagic degradation. This study provides new insights into the mechanisms by which P. gingivalis persists in endothelial cells and its potential role in atherosclerosis progression.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1613366/fullPorphyromonas gingivalisendothelial cellsmitophagylysosomal functionxenophagy |
| spellingShingle | Cheng Zheng Jianmin Huang Shengming Xu Bin Lu Hanxin Que Tianhao Chen Yubo Hou Yubo Hou Linlin He Linlin He Xia Fan Fa-Ming Chen Yi Wang Yi Wang Hui Deng Hui Deng Porphyromonas gingivalis hijacks mitophagy and lysosomal function to persist in endothelial cells Frontiers in Cellular and Infection Microbiology Porphyromonas gingivalis endothelial cells mitophagy lysosomal function xenophagy |
| title | Porphyromonas gingivalis hijacks mitophagy and lysosomal function to persist in endothelial cells |
| title_full | Porphyromonas gingivalis hijacks mitophagy and lysosomal function to persist in endothelial cells |
| title_fullStr | Porphyromonas gingivalis hijacks mitophagy and lysosomal function to persist in endothelial cells |
| title_full_unstemmed | Porphyromonas gingivalis hijacks mitophagy and lysosomal function to persist in endothelial cells |
| title_short | Porphyromonas gingivalis hijacks mitophagy and lysosomal function to persist in endothelial cells |
| title_sort | porphyromonas gingivalis hijacks mitophagy and lysosomal function to persist in endothelial cells |
| topic | Porphyromonas gingivalis endothelial cells mitophagy lysosomal function xenophagy |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1613366/full |
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