Mitochondrial quality control mechanisms as therapeutic targets in doxorubicin-induced cardiotoxicity

Doxorubicin (DOX) is a chemotherapeutic drug that is utilized for solid tumors and hematologic malignancies, but its clinical application is hampered by life-threatening cardiotoxicity including cardiac dilation and heart failure. Mitochon-drial quality control processes, including mitochondrial proteostasis, mitophagy, and mitochondrial dynamics and biogenesis, serve to maintain mitochondrial homeostasis in the cardiovascular system. Importantly, recent advances have unveiled a major role for defective mitochondrial quality control in the etiology of DOX cardiomyopathy. Moreover, specific interventions targeting these quality control mechanisms to preserve mitochondrial function have emerged as poten-tial therapeutic strategies to attenuate DOX cardiotoxicity. However, clinical translation is challenging because of obscure mechanisms of action and potential adverse effects. The purpose of this review is to provide new insights regarding the role of mitochondrial quality control in the pathogenesis of DOX cardiotoxicity, and to explore promising therapeutic approaches targeting these mechanisms to aid clinical management.

Automated summary

Doxorubicin (DOX) is effective in treating solid tumors and hematologic malignancies but its clinical application is limited by its cardiotoxicity. Defective mitochondrial quality control has been found to play a major role in the development of DOX-induced cardiomyopathy. Targeting these quality control mechanisms has emerged as a potential therapeutic strategy to attenuate DOX cardiotoxicity. However, clinical translation is challenging due to obscure mechanisms of action and potential adverse effects.