{
  "abstract": "Sepsis-associated lung injury arises from a dysregulated host response to infection, but the organelle-level mechanisms linking microbial sensing to alveolar–capillary barrier failure remain incompletely resolved. This Review proposes lysosomal pH dysregulation as a candidate, context-dependent signal-amplifying hub rather than a universal initiating event. We synthesize evidence involving V-ATPase-dependent acidification, ClC-7/OSTM1-mediated chloride homeostasis, TMEM175-dependent ion conductance, mTORC1–TFEB signaling, mitochondrial stress, mitochondria–lysosome contact-site proton transfer, and autophagy–lysosome function while distinguishing direct organelle pH measurements from non-equivalent readouts such as membrane permeabilization, cathepsin redistribution, LysoTracker intensity, and autophagic flux. Of 21 formally appraised mechanistic axes, only 2 met Level I criteria; most evidence was Level III or IV and therefore extrapolative or hypothesis-generating. Across macrophages, epithelial cells, pulmonary endothelial cells, and fibroblasts, lysosomal dysfunction may impair pathogen clearance and cellular quality control while amplifying inflammatory signaling and alveolar–capillary barrier injury. We therefore position lysosomal pH homeostasis as a testable mechanistic and stratification axis whose relevance is likely to vary by compartment, cell type, and disease stage.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Critical Care Medicine, The First Affiliated Hospital of Gannan Medical University , ,",
    "Department of Emergency Medicine, The First Affiliated Hospital of Dalian Medical University , ,",
    "Department of Critical Care Medicine, The First Affiliated Hospital of Shihezi University , ,",
    "The First Clinical Medical College, Gannan Medical University , ,",
    "Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University , ,"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Gengjia Tu"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhijie Deng"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuling Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Peigang Tian"
    },
    {
      "affs": [
        0
      ],
      "name": "Yu Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanyan Deng"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhiyuan Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yi Liu"
    },
    {
      "affs": [
        3
      ],
      "name": "Shouwei Zhong"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianjun Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongquan Zhu"
    },
    {
      "affs": [
        4
      ],
      "name": "Jiamin Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianhua Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2bxe2ef97jkpt.bib",
  "cited_by": 0,
  "doi": "10.3389/fcimb.2026.1953667",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13728857/?tool=EBI",
  "id": "2bxe2ef97jkpt",
  "issns": [
    "2235-2988"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13728857",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "1307|Autophagy in Disease and Therapy"
    ]
  ],
  "openalex": "W7223061556",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13728857/pdf/?tool=EBI",
  "pmcid": "PMC13728857",
  "pmid": "42978958",
  "published": "2026-10-20",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/2bxe2ef97jkpt.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:46Z",
      "native_id": "PMC:PMC13728857",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13728857"
    },
    {
      "first_seen": "2026-11-07T12:21:44Z",
      "native_id": "PMC13728857",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcimb.2026.1953667"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Autophagy in Disease and Therapy",
      "subfield": "cell-biology"
    }
  ],
  "title": "Lysosomal pH dysregulation as a candidate signal-amplifying hub in sepsis-associated lung injury",
  "title_text": "Lysosomal pH dysregulation as a candidate signal-amplifying hub in sepsis-associated lung injury",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:44Z",
  "url": "https://research.draconitic.com/paper/2bxe2ef97jkpt",
  "venue": "Frontiers in cellular and infection microbiology",
  "versions": []
}