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神经元轴突线粒体长距离转运的力生物学

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作为极性细胞,神经元由胞体、网状的树突和细长并具有分支的轴突构成。完成分化的神经元在脊椎动物的整个生命周期中要保持正常的生理功能,需要大量的能量来维持静息电位与突触传递。神经元主要依赖于线粒体氧化磷酸化产生的ATP提供能量。神经元通过长距离运输与锚定将健康的线粒体运送并富集到轴突分支突触前末梢等能量消耗较大的区域,同时将轴突末梢老化或受损的线粒体反向转运到胞体进行清除。本文结合作者自己的研究从力学的观点,论述在驱动力作用下线粒体是如何克服阻力在轴突进行长距离运输。综述内容包括微管的极性、微管马达蛋白、线粒体衔接蛋白复合物、线粒体与锚定蛋白相互作用、细胞内阻力、线粒体与内质网的相互作用、线粒体生成、裂变、融合、分裂、质量控制等方面。这些新颖的观点将为认识由线粒体运输障碍引起的神经系统疾病提供重要的参考。
Mechanobiology of Long-distance Mitochondria Transport in Neuronal Axon
As polar cells,neurons are composed of a cell body,dendritic networks,and long,branched axons.To maintain normal physiological functions throughout the lifespan of vertebrates,differentiated neurons require substantial energy to sustain resting potential and synaptic transmission.Neurons predominantly rely on ATP generated through mitochondrial oxidative phosphorylation for energy.They transport and accumulate healthy mitochondria to energy-demanding areas,such as the presynaptic terminals of axon branches,through long-distance transport and anchoring,while reversing the transport of aged or damaged mitochondria in the axon terminals back to the soma for degradation.This article,integrating authors'research,discusses from a mechanical perspective how mitochondria overcome resistance to achieve long-distance transport along axons under the influence of driving forces.The review covers topics such as microtubule polarity,microtubule motor proteins,mitochondrial docking protein complexes,interactions between mitochondria and anchoring proteins,intracellular resistance,interactions between mitochondria and the endoplasmic reticulum,and aspects of mitochondrial biogenesis,fission,fusion,division,and quality control.These novel perspectives will provide important insights for understanding neurological diseases caused by mitochondrial transport dysfunctions.

mitochondrial transportaxondriving forceanchoring

赵虎成、孙艳丽、钱舒乐、冯西桥

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清华大学航天航空学院工程力学系生物力学与医学工程研究所,北京 100084

线粒体转运 轴突 驱动力 锚定

国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金

12072176122115304501203201411921002

2024

生物化学与生物物理进展
中国科学院生物物理研究所,中国生物物理学会

生物化学与生物物理进展

CSTPCD北大核心
影响因子:0.476
ISSN:1000-3282
年,卷(期):2024.51(9)