Pharmacological activation of mitophagy prevents calcific aortic valve disease by targeting dysregulated mitochondrial-to-nuclear communication

Mitophagy is impaired in calcified human aortic valves and during hVIC osteogenic differentiation, and TJ0113 pharmacologically activates MCL1-mediated mitophagy to attenuate CAVD progression.

• Why it matters: CAVD has no pharmacologic therapy, and it was unknown whether mitophagy impairment occurs in calcified valves and during human valvular cell osteogenic differentiation.
• What they did: The study used scRNA-seq on human aortic valves and hVICs, then tested TJ0113 in two CAVD mouse models with multi-omics and functional rescue experiments.
• The result: TJ0113 restored MCL1-PRMT3 mitochondrial binding and reversed dysregulated mitochondrial-to-nuclear communication involving PRMT3, BACH1 nuclear translocation, and PARM1 regulation, implying therapeutic potential to slow disease progression.

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