Fig. 7: Working model.

Epirubicin, inhibiting lysosomal acidification and lysosomal function via decreasing ATP6V0A2 expression, leads to increased ROS production and lipid peroxidation, motivating cardiomyocyte ferroptosis and induces cardiac injury. Maintenance of lysosomal acidification by increasing ATP6V0A2 partially blunts ferroptosis and protects heart from eEIC.