TMEM38A基因敲除HEK293细胞

TRIC-A is an intracellular cation channel enriched in excitable tissues that is recently identified as a key modulator of sarcoplasmic reticulum (SR) Ca homeostasis through direct interaction with type 2 ryanodine receptors (RyR). Given the intimate anatomical and functional coupling between the SR and mitochondria, we investigated whether TRIC-A contributes to SR-mitochondrial crosstalk under cardiac stress conditions. Using a transverse aortic constriction (TAC) model, we found that TRIC-A mice developed more severe cardiac hypertrophy, underwent maladaptive remodeling, and activated apoptotic pathways compared with wild-type littermates. At the cellular level, TRIC-A-deficient cardiomyocytes were more susceptible to HO-induced mitochondrial injury and displayed abnormal mitochondrial morphology. Live-cell imaging revealed exaggerated mitochondrial Ca uptake during caffeine stimulation and increased propensity for store-overload-induced Ca release (SOICR). Complementary studies in HEK293 cells expressing RyR demonstrated that exogenous TRIC-A expression attenuates RyR-mediated mitochondrial Ca overload, preserves respiratory function, and suppresses superoxide generation. Together, these findings identify TRIC-A as a critical regulator of SR-mitochondrial Ca signaling. By constraining mitochondrial Ca influx and limiting oxidative stress, TRIC-A safeguards cardiomyocytes against SOICR-driven injury and confers protection against pressure overload-induced cardiac dysfunction.