Laboratory of Psychobiology, Department of Neuroscience, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Haifa 31096, Israel.
Cells. 2024 Feb 27;13(5):410. doi: 10.3390/cells13050410.
Mitochondria, the energy suppliers of the cells, play a central role in a variety of cellular processes essential for survival or leading to cell death. Consequently, mitochondrial dysfunction is implicated in numerous general and CNS disorders. The clinical manifestations of mitochondrial dysfunction include metabolic disorders, dysfunction of the immune system, tumorigenesis, and neuronal and behavioral abnormalities. In this review, we focus on the mitochondrial role in the CNS, which has unique characteristics and is therefore highly dependent on the mitochondria. First, we review the role of mitochondria in neuronal development, synaptogenesis, plasticity, and behavior as well as their adaptation to the intricate connections between the different cell types in the brain. Then, we review the sparse knowledge of the mechanisms of exogenous mitochondrial uptake and describe attempts to determine their half-life and transplantation long-term effects on neuronal sprouting, cellular proteome, and behavior. We further discuss the potential of mitochondrial transplantation to serve as a tool to study the causal link between mitochondria and neuronal activity and behavior. Next, we describe mitochondrial transplantation's therapeutic potential in various CNS disorders. Finally, we discuss the basic and reverse-translation challenges of this approach that currently hinder the clinical use of mitochondrial transplantation.
线粒体是细胞的能量供应者，在许多对生存至关重要或导致细胞死亡的细胞过程中发挥着核心作用。因此，线粒体功能障碍与许多全身性和中枢神经系统疾病有关。线粒体功能障碍的临床表现包括代谢紊乱、免疫系统功能障碍、肿瘤发生以及神经元和行为异常。在这篇综述中，我们重点关注线粒体在中枢神经系统中的作用，中枢神经系统具有独特的特征，因此高度依赖于线粒体。首先，我们回顾了线粒体在神经元发育、突触发生、可塑性和行为以及它们适应大脑中不同细胞类型之间复杂连接中的作用。然后，我们回顾了对外源性线粒体摄取机制的了解甚少，并描述了确定其半衰期和对神经元发芽、细胞蛋白质组和行为的长期移植效果的尝试。我们进一步讨论了线粒体移植作为研究线粒体与神经元活动和行为之间因果关系的工具的潜力。接下来，我们描述了线粒体移植在各种中枢神经系统疾病中的治疗潜力。最后，我们讨论了目前阻碍线粒体移植临床应用的该方法的基础和逆向翻译挑战。
