Park Ji-Hyun, Hayakawa Kazuhide
Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States.
Front Cell Dev Biol. 2021 Mar 5;9:642853. doi: 10.3389/fcell.2021.642853. eCollection 2021.
Mitochondria actively participate in the regulation of cell respiratory mechanisms, metabolic processes, and energy homeostasis in the central nervous system (CNS). Because of the requirement of high energy, neuronal functionality and viability are largely dependent on mitochondrial functionality. In the context of CNS disorders, disruptions of metabolic homeostasis caused by mitochondrial dysfunction lead to neuronal cell death and neuroinflammation. Therefore, restoring mitochondrial function becomes a primary therapeutic target. Recently, accumulating evidence suggests that active mitochondria are secreted into the extracellular fluid and potentially act as non-cell-autonomous signals in CNS pathophysiology. In this mini-review, we overview findings that implicate the presence of cell-free extracellular mitochondria and the critical role of intercellular mitochondrial transfer in various rodent models of CNS disorders. We also discuss isolated mitochondrial allograft as a novel therapeutic intervention for CNS disorders.
线粒体积极参与中枢神经系统(CNS)中细胞呼吸机制、代谢过程和能量稳态的调节。由于对高能量的需求,神经元的功能和活力在很大程度上依赖于线粒体的功能。在中枢神经系统疾病的背景下,线粒体功能障碍导致的代谢稳态破坏会导致神经元细胞死亡和神经炎症。因此,恢复线粒体功能成为主要的治疗靶点。最近,越来越多的证据表明,活性线粒体被分泌到细胞外液中,并可能在中枢神经系统病理生理学中作为非细胞自主信号发挥作用。在本综述中,我们概述了在各种啮齿动物中枢神经系统疾病模型中涉及无细胞细胞外线粒体的存在以及细胞间线粒体转移的关键作用的研究结果。我们还讨论了分离的线粒体同种异体移植作为中枢神经系统疾病的一种新型治疗干预措施。