Figure 2.

Effects of exercise on mitochondrial processes involved in doxorubicin (DOX)-associated cardiotoxicity. Exercise increases expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) which binds to nuclear respiratory factors (Nrf1/2) and induces mitochondrial transcription factor A (TFAM) expression. Mitochondrial translocation of TFAM contributes to mitochondrial biogenesis. Exercise may reduce DOX accumulation in mitochondria by increasing expression of ATP-binding cassette (ABC) transporters (ABCB6, ABCB7, ABCB8 and ABCB10). Exercise increases Nrf2 expression, which is known to activate the antioxidant response element (ARE) and antioxidant gene expression. Antioxidants inhibit reactive oxygen species (ROS)-induced mitochondrial membrane permeability transition pore (MPTP) opening, a process that releases pro-apoptotic Bax and accumulates calcium (Ca²⁺). Image created with Biorender.com.