Disruption of cTnT-Mediated Sarcomere–Mitochondrial Communication Results in Dilated Cardiomyopathy

Our findings delineate a novel pathogenic mechanism underlying DCM, demonstrating that cTnT (p.K185E) sequence variation disrupts sarcomere-mitochondrial communication by weakening the interaction between cTnT and 14-3-3 proteins, thereby accelerating mitochondrial fragmentation through excessive activation of the 14-3-3 protein-mediated RAS/RAF1-p44/42-DRP1/MFF signaling axis. Therefore, therapeutic targeting of 14-3-3 proteins and p44/42 kinase activity may represent a promising strategy for DCM and other cardiac diseases associated with aberrant mitochondrial dynamics.