阿霉素是一种被广泛使用的有效抗癌药物。然而，阿霉素的使用也与部分患者的心脏毒性副作用有关。研究显示，线粒体损伤是阿霉素诱发心肌损伤的病理机制之一。在本研究中，我们证明线粒体移植可以通过直接提供功能性线粒体来抑制阿霉素诱导的心肌毒性。线粒体移植改善了心肌细胞的收缩功能和呼吸能力，减少了细胞凋亡和氧化应激。从多种来源分离的线粒体，包括小鼠心脏、小鼠和人类动脉血液以及人类诱导多能干细胞心肌细胞（hiPSC-CMs）衍生的线粒体，都具有类似的心脏保护作用。在机械上，线粒体移植通过激活阿霉素处理的小鼠心脏中的谷氨酰胺代谢，并阻断谷氨酰胺代谢可减弱线粒体移植的心脏保护作用。总体而言，我们的研究表明，从动脉血液中分离的线粒体可用于线粒体移植，这可能成为治疗阿霉素诱导的心脏毒性的可行的有前途的治疗选择。© 2023 作者

Doxorubicin is a wildly used effective anticancer agent. However, doxorubicin use is also related to cardiotoxic side effect in some patients. Mitochondrial damage has been shown to be one of the pathogeneses of doxorubicin-induced myocardial injury. In this study, we demonstrated that mitochondrial transplantation could inhibit doxorubicin-induced cardiotoxicity by directly supplying functional mitochondria. Mitochondrial transplantation improved contractile function and respiratory capacity, reduced cellular apoptosis and oxidative stress in cardiomyocytes. Mitochondria isolated from various sources, including mouse hearts, mouse and human arterial blood, and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), all exerted similar cardioprotective effects. Mechanically, mitochondrial transplantation activates glutamine metabolism in doxorubicin-treated mice heart and blocking glutamine metabolism attenuated the cardioprotective effects of mitochondrial transplantation. Overall, our study demonstrates that mitochondria isolated from arterial blood could be used for mitochondrial transplantation, which might serve as a feasible promising therapeutic option for patients with doxorubicin-induced cardiotoxicity.© 2023 The Author(s).