Zhang Heng, Xie Saiyang, Deng Wei
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Hubei Key Laboratory of Metabolism and Related Chronic Diseases, Wuhan 430060, China.
Biomolecules. 2024 Dec 17;14(12):1614. doi: 10.3390/biom14121614.
Doxorubicin is a chemotherapeutic drug utilized for solid tumors and hematologic malignancies, but its clinical application is hampered by life-threatening cardiotoxicity, including cardiac dilation and heart failure. Mitophagy, a cargo-specific form of autophagy, is specifically used to eliminate damaged mitochondria in autophagosomes through hydrolytic degradation following fusion with lysosomes. Recent advances have unveiled a major role for defective mitophagy in the etiology of DOX-induced cardiotoxicity. Moreover, specific interventions targeting this mechanism to preserve mitochondrial function have emerged as potential therapeutic strategies to attenuate DOX-induced cardiotoxicity. However, clinical translation is challenging because of the unclear mechanisms of action and the potential for pharmacological adverse effects. This review aims to offer fresh perspectives on the role of mitophagy in the development of DOX-induced cardiotoxicity and investigate potential therapeutic strategies that focus on this mechanism to improve clinical management.
阿霉素是一种用于实体瘤和血液系统恶性肿瘤的化疗药物，但其临床应用受到危及生命的心脏毒性的阻碍，包括心脏扩张和心力衰竭。线粒体自噬是自噬的一种货物特异性形式，它专门用于通过与溶酶体融合后的水解降解来清除自噬体中受损的线粒体。最近的研究进展揭示了缺陷线粒体自噬在阿霉素诱导的心脏毒性病因中的主要作用。此外，针对这一机制以维持线粒体功能的特异性干预措施已成为减轻阿霉素诱导的心脏毒性的潜在治疗策略。然而，由于作用机制尚不清楚以及存在药理不良反应的可能性，临床转化具有挑战性。本综述旨在就线粒体自噬在阿霉素诱导的心脏毒性发展中的作用提供新的观点，并研究专注于该机制以改善临床管理的潜在治疗策略。
