In the I/R model of hippocampus cells, MCU up‐regulated the expression of mitochondrial fission–related protein Drp1/Fis1/MIEF and promoted mitochondrial fission.21 In pressure overload‐induced heart failure model, MCU is up‐regulated and inhibited mitophagy.22 In this study, through the intervention of inhibitor Ru360 and agonist spermine on MCU function, we demonstrated that MCU promoted Drp1 to migrate to mitochondria; down‐regulated OPA1, PARKIN and mito‐LC3II; and played a role in promoting mitochondrial fission, inhibiting mitochondrial fusion and mitophagy. The gene discussed is OPA1; the disease is heart failure.