TRMT10C promotes mitochondrial fission through transferrin receptor m1A methylation modification and aggravates the progression of atrial fibrillation

Atrial fibrillation (AF) is a common cardiac arrhythmia often accompanied by structural remodeling of the atria, particularly fibrosis, and disruption of normal mitochondrial function. N(1)‐methyladenosine (m1A), a methylation of RNA, is gaining attention for its role in diverse biological processes. This study aimed to explore the role of the m1A methyltransferase tRNA methyltransferase 10C (TRMT10C) in AF pathogenesis. In the study, TRMT10C and m1A methylation levels were upregulated in AF rats, accompanied by excessive mitochondrial fission and myocardial fibrosis. Knockdown of TRMT10C inhibited the expression levels of mitochondrial fission‐related proteins Drp1 and Fis1, reduced collagen deposition (collagen I, Postn, collagen III, and fibronectin), and AF progression. In vitro results showed that TRMT10C knockdown inhibited TGF‐β1‐induced cardiac fibroblasts proliferation and migration, whereas overexpression of transferrin receptor (TFRC) reversed this effect. Mechanistically, TRMT10C enhanced the stability of TFRC mRNA by promoting m1A methylation, driving mitochondrial fission and fibrosis. Collectively, our findings elucidate a novel TRMT10C–TFRC m 1 A axis driving pathological mitochondrial dynamics and fibrosis in AF, offering new insight into cell‐signaling pathways underlying atrial disease and potential therapeutic targets.