Optimizing mitochondrial maintenance in extended neuronal projections
Optimizing mitochondrial maintenance in extended neuronal projections
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DOI：
10.1101/2020.09.11.294207
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发表时间：
2020-09
影响因子：
4.3
通讯作者：
Anamika Agrawal;Elena F. Koslover
中科院分区：
文献类型：
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作者：
Anamika Agrawal;Elena F. Koslover
神经元依赖于局部线粒体来满足空间异质性代谢需求。线粒体老化发生的时间尺度短于神经元的寿命，需要运输新鲜的材料从索马。维持健康线粒体的最佳分布需要定位于高代谢需求位点的固定池与能够递送新物质的运动池之间的相互作用。这些池之间的交换可以通过瞬时融合/裂变事件或通过停止和重新启动整个线粒体来发生。我们的定量模型的神经元有丝分裂，确定关键参数，管理稳态线粒体健康的离散位置。固定池和活动池之间很少交换，优化了该系统。通过瞬时融合的交换允许稳健的维持，这可以通过线粒体自噬的选择性再循环来进一步改善。这些结果提供了一个框架，用于量化细胞器运输和相互作用中的扰动如何影响神经元中的线粒体稳态，这是许多神经退行性疾病的关键方面。
Neurons rely on localized mitochondria to fulfill spatially heterogeneous metabolic demands. Mi-tochondrial aging occurs on timescales shorter than the neuronal lifespan, necessitating transport of fresh material from the soma. Maintaining an optimal distribution of healthy mitochondria requires an interplay between a stationary pool localized to sites of high metabolic demand and a motile pool capable of delivering new material. Interchange between these pools can occur via transient fusion / fission events or by halting and restarting entire mitochondria. Our quantitative model of neuronal mitostasis identifies key parameters that govern steady-state mitochondrial health at discrete locations. Very infrequent exchange between stationary and motile pools optimizes this system. Exchange via transient fusion allows for robust maintenance, which can be further improved by selective recycling through mitophagy. These results provide a framework for quantifying how perturbations in organelle transport and interactions affect mitochondrial homeostasis in neurons, an key aspect underlying many neurodegenerative disorders.