MG53 mediates skeletal muscle-liver cross-talk and enhances alcohol metabolism in alcoholic liver disease
Alcoholic liver disease (ALD) remains a significant clinical challenge with limited therapeutics. It is strongly associated with sarcopenia, which further worsens the prognosis in liver cirrhosis. Zinc-deficiency is a hallmark of ALD, impairing the liver's antioxidant defenses and alcohol metabolism. Here we identify a chaperone role for MG53/TRIM72 in facilitating crosstalk between zinc and alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH2), acting as a metabolic regulator of muscle-liver communication. In ALD, muscle-derived MG53 is transported to liver and mitigates liver damage. MG53 deficiency exacerbates hepatic zinc-deficiency and impairs ADH and ALDH2 activity, which are reversed by systemic administration of recombinant human MG53 (rhMG53). MG53's B-box motif coordinates zinc interaction with ADH and ALDH2, enhancing their enzymatic activity to clear toxic alcohol byproducts. We developed a bio-derived nanoparticle for co-delivery of rhMG53 and zinc, offering a promising therapeutic approach for ALD. In vivo findings are applicable to the male sex only.
Authors
- P Chen
- Jianjie Ma (ORCID: https://orcid.org/0000-0003-3865-6112)
- Y. Wang
- Jun Xie (ORCID: https://orcid.org/0000-0002-6242-8454)
- Mingming Zhang (ORCID: https://orcid.org/0000-0001-8480-0280)
- J. Wang (ORCID: https://orcid.org/0000-0001-9684-7983)
- Ming Tang (ORCID: https://orcid.org/0000-0003-1587-2584)
- Ying Jiang (ORCID: https://orcid.org/0000-0002-2161-3952)
- Lintao Jiang
- Kyung Eun Lee (ORCID: https://orcid.org/0000-0001-6689-2759)
- Xindi Zeng
- H Jiang
- Ning Liu
- Yujia Ye
- Linfei Zhang
- Lingzhi Yang
- Yu Han
- Jongsoo Kim
- Dandong Fang
- Chunyu Zeng
- Rongning Liu
- Yuchen Chen (ORCID: https://orcid.org/0000-0001-8558-3062)
- Tingting Shu
- Bo He
Institutions
- Army Medical University (CN)
- Chongqing University (CN)
- Kunming Medical University (CN)
- Wenzhou Medical University (CN)
- Nanjing General Hospital of Nanjing Military Command (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- Affiliated Hospital of Southwest Medical University (CN)
- Daping Hospital (CN)
- Ministry of Education (RO)
- Ministry of Education (SA)
- First Affiliated Hospital of Kunming Medical University (CN)
- University of Chinese Academy of Sciences (CN)
- University of Virginia (US)
- Chongqing Medical University (CN)
- Nanjing University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-02-13
- DOI
- https://doi.org/10.1038/s41467-026-69132-6
- Citations
- 1
- Primary Topic
- Alcohol Consumption and Health Effects
- Type
- article
- Field-Weighted Citation Impact
- 36.00