Puerarin Targets MIC19 to Suppress Mitochondrial Metabolism of Tumor-Infiltrating Tregs and Enhance Anti-tumor Immunity.

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 antitumo

SUBMITTER: Li Y 

PROVIDER: S-EPMC12822449 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature