Mitochondrial Sirtuins and Doxorubicin-induced Cardiotoxicity
Mitochondrial Sirtuins and Doxorubicin-induced Cardiotoxicity
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DOI：
10.1007/s12012-020-09626-x
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发表时间：
2021-01-12
影响因子：
3.2
通讯作者：
Li, Juxiang
中科院分区：
文献类型：
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作者：
He, Ling;Liu, Fuxiang;Li, Juxiang
阿霉素 (DOX) 是许多肿瘤最有效且广泛使用的治疗方法。然而，其心脏毒性阻碍了其临床应用。 DOX诱导的线粒体功能障碍，导致活性氧（ROS）产生、心肌细胞死亡、生物能衰竭和心脏功能下降，是心脏毒性的一个非常重要的机制。这些细胞过程均通过线粒体 Sirtuins (SIRT3-SIRT4) 连接。线粒体 Sirtuins 通过增加线粒体代谢、通过激活抗氧化酶锰依赖性超氧化物歧化酶 (MnSOD) 抑制 ROS 生成、通过激活叉头同源盒 O 型 (FOXO) 和 P53 途径减少细胞凋亡以及通过 AMP 激活蛋白激酶 (AMPK)/mTOR 信号传导增加自噬来保护线粒体功能。因此，sirtuins 在涉及 DOX 诱导的心脏毒性的许多机制的控制点发挥作用。在这篇综述中，我们重点关注线粒体去乙酰化酶在线粒体生物学和阿霉素诱导的心脏毒性中的作用。进一步的目标是强调其他线粒体过程，例如自噬（线粒体自噬）和线粒体质量控制（MQC），其中线粒体去乙酰化酶对心脏毒性的影响尚不清楚。
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.