Campbell Graham R, Mahad Don J
Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Autoimmune Dis. 2011 Feb 8;2011:262847. doi: 10.4061/2011/262847.
Mitochondria are the most efficient producers of energy in the form of ATP. Energy demands of axons, placed at relatively great distances from the neuronal cell body, are met by mitochondria, which when functionally compromised, produce reactive oxygen species (ROS) in excess. Axons are made metabolically efficient by myelination, which enables saltatory conduction. The importance of mitochondria for maintaining the structural integrity of myelinated axons is illustrated by neuroaxonal degeneration in primary mitochondrial disorders. When demyelinated, the compartmentalisation of ion channels along axons is disrupted. The redistribution of electrogenic machinery is thought to increase the energy demand of demyelinated axons. We review related studies that focus on mitochondria within unmyelinated, demyelinated and dysmyelinated axons in the central nervous system. Based on neuropathological observations we propose the increase in mitochondrial presence within demyelinated axons as an adaptive process to the increased energy need. An increased presence of mitochondria would also increase the capacity to produce deleterious agents such as ROS when functionally compromised. Given the lack of direct evidence of a beneficial or harmful effect of mitochondrial changes, the precise role of increased mitochondrial presence within axons due to demyelination needs to be further explored in experimental demyelination in-vivo and in-vitro.
线粒体是以ATP形式存在的最有效的能量生产者。轴突与神经元细胞体相距较远，其能量需求由线粒体满足，当线粒体功能受损时，会产生过量的活性氧（ROS）。髓鞘形成使轴突在代谢上更高效，从而实现跳跃式传导。原发性线粒体疾病中的神经轴突退变说明了线粒体对维持有髓轴突结构完整性的重要性。脱髓鞘时，轴突上离子通道的分隔会被破坏。人们认为，电生机制的重新分布会增加脱髓鞘轴突的能量需求。我们综述了相关研究，这些研究聚焦于中枢神经系统中无髓鞘、脱髓鞘和髓鞘发育异常的轴突内的线粒体。基于神经病理学观察，我们提出脱髓鞘轴突中线粒体数量增加是对能量需求增加的一种适应性过程。线粒体数量增加也会在功能受损时增加产生ROS等有害物质的能力。鉴于缺乏线粒体变化有益或有害影响的直接证据，脱髓鞘导致轴突内线粒体数量增加的确切作用需要在体内和体外实验性脱髓鞘中进一步探索。
