Pacak Christina A, Preble Janine M, Kondo Hiroshi, Seibel Peter, Levitsky Sidney, Del Nido Pedro J, Cowan Douglas B, McCully James D
Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32607, USA.
Division of Cardiac Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Biol Open. 2015 Apr 10;4(5):622-6. doi: 10.1242/bio.201511478.
Previously, we have demonstrated that the transplantation of viable, structurally intact, respiration competent mitochondria into the ischemic myocardium during early reperfusion significantly enhanced cardioprotection by decreasing myocellular damage and enhancing functional recovery. Our in vitro and in vivo studies established that autologous mitochondria are internalized into cardiomyocytes following transplantation; however, the mechanism(s) modulating internalization of these organelles were unknown. Here, we show that internalization of mitochondria occurs through actin-dependent endocytosis and rescues cell function by increasing ATP content and oxygen consumption rates. We also show that internalized mitochondria replace depleted mitochondrial (mt)DNA. These results describe the mechanism for internalization of mitochondria within host cells and provide a basis for novel therapeutic interventions allowing for the rescue and replacement of damaged or impaired mitochondria.
此前，我们已经证明，在早期再灌注期间将存活的、结构完整且具有呼吸功能的线粒体移植到缺血心肌中，可通过减少心肌细胞损伤和增强功能恢复显著增强心脏保护作用。我们的体外和体内研究表明，自体线粒体在移植后会被心肌细胞内化；然而，调节这些细胞器内化的机制尚不清楚。在这里，我们表明线粒体的内化通过肌动蛋白依赖性内吞作用发生，并通过增加ATP含量和氧消耗率来挽救细胞功能。我们还表明，内化的线粒体替代了耗尽的线粒体（mt）DNA。这些结果描述了线粒体在宿主细胞内内化的机制，并为新型治疗干预提供了基础，从而实现对受损或功能障碍线粒体的挽救和替代。
