{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:49:11Z","timestamp":1793836151672,"version":"4.6.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      The direct infection of endothelial cells by\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      (\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      ), 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\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      hijacks mitophagy and lysosomes to persist in endothelial cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Human aortic endothelial cells (HAECs) were infected with\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      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\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      intracellular survival were evaluated by antibiotic protection assays and SYTO-9 staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our data demonstrated that\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      initiates PTEN\u00adinduced 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\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      promotes its intracellular survival in endothelial cells by initiating mitophagy and impairing lysosomal function. Furthermore, the mitophagy activator decreased the co-localization of\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      with microtubule-associated protein 1 light chain 3 (LC3)-p62, LC3-NDP52, and lysosomal-associated membrane protein 1 (LAMP1), suggesting that\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      -initiated mitophagy inhibited xenophagosome formation and autophagosome\/xenophagosome-lysosome fusion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings reveal that\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      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\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      persists in endothelial cells and its potential role in atherosclerosis progression.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1613366","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T05:27:44Z","timestamp":1754630864000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Porphyromonas gingivalis hijacks mitophagy and lysosomal function to persist in endothelial cells"],"prefix":"10.3389","volume":"15","author":[{"given":"Cheng","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengming","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanxin","family":"Que","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubo","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fa-Ming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/s41580-019-0185-4","article-title":"Lysosomes as dynamic regulators of cell and organismal homeostasis","volume":"21","author":"Ballabio","year":"2020","journal-title":"Nat. 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