Endoplasmic Reticulum Stress Induced by Turbulence of Mitochondrial Fusion and Fission Was Involved in Isoproterenol-Induced H9c2 Cell Injury

Alterations in mitochondrial fusion and fission dynamics are critical determinants of cellular fate. However, how stress-induced mitochondrial fusion and fission affect the physiological and pathological processes in cardiomyocytes remains poorly understood. Based on an established in vitro model of stress-induced cardiomyocyte injury using isoproterenol-treated H9c2 cells, this study aimed to investigate whether the dysregulation of mitochondrial dynamics-specifically, an imbalance between fusion and fission-activates the IRE1α-ASK1-JNK endoplasmic reticulum stress signaling pathway, thereby contributing to cardiomyocyte damage. Under this experimental paradigm, cell viability was evaluated using the CCK-8 assay. Concurrently, immunofluorescence staining was employed to assess reactive oxygen species accumulation, the expression of key mitochondrial fusion/fission proteins, and components of the ER stress pathway (IRE1α, ASK1, and JNK). Results demonstrated that isoproterenol treatment elevated intracellular ROS levels and induced significant changes in both mitochondrial dynamics-related proteins and the IRE1α-ASK1-JNK signaling axis. In contrast, administration of the mitochondrial fission inhibitor Mdivi-1 attenuated ROS accumulation, restored the expression of the affected proteins toward normal levels, and alleviated cardiomyocyte injury. Collectively, these findings indicate that the disruption of mitochondrial fusion/fission dynamics triggers endoplasmic reticulum stress via the IRE1α-ASK1-JNK cascade, which participates in the pathological progression of cardiomyocyte injury.