ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Puerarin Targets MIC19 to Suppress Mitochondrial Metabolism of Tumor-Infiltrating Tregs and Enhance Anti-tumor Immunity.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Pickering Emulsion Stabilized byFoods (Basel, Switzerland) · 2026Article
- Article
- CHCHD3(MIC19): mitochondrial cristae structure regulation and disease associations.Frontiers in molecular biosciences · 2026Review
- Immunosuppressive cells as barriers to cancer therapy: mechanisms and emerging solutions.Frontiers in immunology · 2026Review
- Puerarin Targets MIC19 to Suppress Mitochondrial Metabolism of Tumor-Infiltrating Tregs and Enhance Anti-tumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrative multi-omics analysis prioritizes ALDH2 as a candidate Puerarin-associated target linked to macrophage infiltration in lung adenocarcinoma.Frontiers in immunology · 2026Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Regulatory T cells (Tregs) are pivotal mediators of immunosuppression in hepatocellular carcinoma, but strategies for selectively disrupting their function remain underdeveloped. Here, puerarin, a natural isoflavone is identifed as a selective immunometabolic modulator. It impairs mitochondrial metabolism in tumor-infiltrating Tregs (Ti-Tregs) without affecting conventional T cells. Mechanistically, puerarin directly binds to MIC19-a core subunit of the mitochondrial contact site and cristae organizing system-leading to its degradation and disruption of the MIC19-MIC60 complex. This disruption causes cristae disorganization, reduces oxidative phosphorylation, and weakens the immunosuppressive function of Ti-Tregs. In vivo, puerarin decreases Ti-Treg infiltration, thereby enhancing antitumor immunity without causing systemic toxicity. Furthermore, MIC19 knockdown and site-directed mutagenesis studies validate the role of critical MIC19 residues (His180, Gln187, and Tyr211) in puerarin's activity. These results reveal a mechanism by which puerarin suppresses mitochondrial metabolism of Ti-Tregs and emphasize the therapeutic potential of natural compounds in metabolic targeting for cancer immunotherapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.