Effects of doxorubicin‐induced cardiotoxicity on cardiac mitochondrial dynamics and mitochondrial function: Insights for future interventions

Figures

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  Figure 1. The effects of doxorubicin on cardiac mitochondrial dynamics and mitochondrial function. Doxorubicin inhibits mitochondrial fusion proteins (MFN1, MFN2 and OPA1) and promotes mitochondrial fission by increasing DRP1 phosphorylation. Doxorubicin undergoes redox cycling and generation of ROS. ROS, in turn, induces lipid peroxidation at cellular membrane and targets subcellular organelle causing mitochondrial DNA damage and decreases mitochondrial transmembrane potential. Doxorubicin inhibits electron transport chain proteins subunit I, II, IV and induces mPTP opening which initiates apoptotic signalling pathway. In addition, doxorubicin binds to topoisomerase IIβ in the nucleus causing DNA double‐stranded breaks and induces apoptosis. Dox, Doxorubicin; MDA, Malondialdehyde; mPTP, mitochondrial permeability transition pore; mtDNA, Mitochondrial DNA; ROS, Reactive oxygen species; ΔΨm, Mitochondrial transmembrane potential

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  Figure 2. The effects of pharmacological and non‐pharmacological interventions on mitochondrial biogenesis, mitochondrial dynamics and mitochondrial function. Various pharmacological interventions have been shown to attenuate apoptosis by promoting mitochondrial function. The CVB‐D promotes mitochondrial biogenesis by preservation of PGC1α and mitochondrial DNA copy number. Balancing the mitochondrial dynamics by increasing mitochondrial fusion proteins and inhibiting mitochondrial fission process also attenuates ROS production and apoptosis. BNIP3, BCL2/adenovirus E1B 19 kD protein‐interacting protein 3; CsA, Cyclosporin A; CVB‐D, Cycloverobuxine‐D; EA, Ellagic acid; LCZ696, Sacubitril/valsartan; Mt, Mitochondria; mPTP, mitochondrial permeability transition pore; mtDNA, Mitochondrial DNA; RESV, Resveratrol; ROS, Reactive oxygen species; SIRT3, Sirtuin3; SOD2, Superoxide dismutase‐2; ΔΨm, Mitochondrial transmembrane potential