{
  "abstract": "Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, yet no standardized pharmacotherapy has been approved for clinical use. The autophagy-lysosome pathway (ALP) serves as an essential intracellular degradation and recycling machinery that sustains hepatic metabolic homeostasis via modulation of lipid turnover, mitochondrial quality surveillance, and hepatocellular detoxification. Accumulating evidence demonstrates that ALP impairment acts as a core pathogenic factor across all stages of MASLD progression. This review systematically elaborates the molecular framework of the ALP and its multifaceted physiological functions in the liver, with special attention to the central pathogenic mechanisms underlying ALP impairment in MASLD: lysosomal dysfunction, defective autophagosome-lysosome fusion, dysregulation of key transcriptional and epigenetic regulators, and impaired subtypes of selective autophagy. ALP activity displays stage-specific characteristics across MASLD progression, featuring compensatory activation in simple hepatic steatosis but functional suppression in metabolic dysfunction-associated steatohepatitis (MASH). Hepatocytes and hepatic stellate cells exert opposing autophagic activity during liver fibrogenesis. We further summarize existing therapeutic strategies targeting the ALP, which fall into three categories: pharmacological agents (ALP agonists, lysosomal modulators, natural bioactive compounds, and nano-drug delivery systems), non-pharmacological interventions (dietary adjustment, physical exercise, and lifestyle modification), and gut-liver axis regulatory approaches. Finally, we address the primary translational bottlenecks and prospective avenues for converting these mechanistic findings into viable clinical therapies.",
  "abstract_shown": true,
  "affiliations": [
    "The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, China.",
    "Medical College, Henan University of Chinese Medicine, Zhengzhou, China.",
    "Henan Medical College, Zhengzhou, China.",
    "The First Affiliated Hospital of Henan University of TCM, Zhengzhou, China.",
    "The Second Affiliated Hospital of Henan University of TCM, Zhengzhou, China."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shuaibing Cao"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinyue Cheng"
    },
    {
      "affs": [
        1
      ],
      "name": "Yi Yang"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Baoping Lu"
    },
    {
      "affs": [
        1
      ],
      "name": "Shan Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Chuntian Huang"
    },
    {
      "affs": [
        3
      ],
      "name": "Mingyu Ba"
    },
    {
      "affs": [
        4
      ],
      "name": "Lei Luo"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Changpu Zhao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1y8ntj5mbbfad.bib",
  "cited_by": 0,
  "doi": "10.3389/fmed.2026.1961366",
  "fulltext_url": "https://europepmc.org/articles/PMC13714512",
  "id": "1y8ntj5mbbfad",
  "issns": [
    "2296-858X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42953075",
  "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",
      "2713|Autophagy in Disease and Therapy"
    ]
  ],
  "openalex": "W7221769989",
  "pdf_url": "https://europepmc.org/articles/PMC13714512?pdf=render",
  "pmcid": "PMC13714512",
  "pmid": "42953075",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/1y8ntj5mbbfad.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42953075",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42953075"
    },
    {
      "first_seen": "2026-11-01T12:21:59Z",
      "native_id": "PMC13714512",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fmed.2026.1961366"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Autophagy in Disease and Therapy",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Autophagy-lysosome pathway dysfunction in MASLD progression: molecular mechanisms and therapeutic targets.",
  "title_text": "Autophagy-lysosome pathway dysfunction in MASLD progression: molecular mechanisms and therapeutic targets.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:59Z",
  "url": "https://research.draconitic.com/paper/1y8ntj5mbbfad",
  "venue": "Frontiers in medicine",
  "versions": []
}