1. Mitochondrial Sirtuins and Doxorubicin-induced Cardiotoxicity
- Author
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Ling He, Juxiang Li, and Fuxiang Liu
- Subjects
Heart Diseases ,Apoptosis ,030204 cardiovascular system & hematology ,Toxicology ,Mitochondria, Heart ,Superoxide dismutase ,03 medical and health sciences ,0302 clinical medicine ,Mitophagy ,Animals ,Humans ,Sirtuins ,Myocytes, Cardiac ,Protein kinase A ,Molecular Biology ,chemistry.chemical_classification ,Reactive oxygen species ,Cardiotoxicity ,Antibiotics, Antineoplastic ,biology ,Autophagy ,AMPK ,Cell biology ,Oxidative Stress ,chemistry ,Doxorubicin ,030220 oncology & carcinogenesis ,biology.protein ,Energy Metabolism ,Reactive Oxygen Species ,Cardiology and Cardiovascular Medicine - Abstract
Doxorubicin (DOX) is the most effective and extensively used treatment for many tumors. However, its clinical use is hampered by its cardiotoxicity. DOX-induced mitochondrial dysfunction, which causes reactive oxygen species (ROS) generation, cardiomyocyte death, bioenergetic failure, and decreased cardiac function, is a very important mechanism of cardiotoxicity. These cellular processes are all linked by mitochondrial sirtuins (SIRT3-SIRT4). Mitochondrial sirtuins preserve mitochondrial function by increasing mitochondrial metabolism, inhibiting ROS generation by activating the antioxidant enzyme manganese-dependent superoxide dismutase (MnSOD), decreasing apoptosis by activating the forkhead homeobox type O (FOXO) and P53 pathways, and increasing autophagy through AMP-activated protein kinase (AMPK)/mTOR signaling. Thus, sirtuins function at the control point of many mechanisms involved in DOX-induced cardiotoxicity. In this review, we focus on the role of mitochondrial sirtuins in mitochondrial biology and DOX-induced cardiotoxicity. A further aim is to highlight other mitochondrial processes, such as autophagy (mitophagy) and mitochondrial quality control (MQC), for which the effect of mitochondrial sirtuins on cardiotoxicity is unknown.
- Published
- 2021
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