Progressive Decrease of Mitochondrial Motility during Maturation of Cortical Axons In Vitro and In Vivo.
Progressive Decrease of Mitochondrial Motility during Maturation of Cortical Axons In Vitro and In Vivo.
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DOI：
10.1016/j.cub.2016.07.064
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发表时间：
2016-10-10
期刊：
影响因子：
--
通讯作者：
Polleux F
中科院分区：
文献类型：
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作者：
Lewis TL Jr;Turi GF;Kwon SK;Losonczy A;Polleux F
大量神经退行性疾病与线粒体功能或运输破坏相关，线粒体对神经元功能的重要性显而易见（综述见[1, 2]）。线粒体对于正常的生物功能至关重要，因为它们能够通过氧化磷酸化产生 ATP、缓冲细胞质钙、调节脂质生物合成并触发细胞凋亡（综述见 [2]）。鉴于神经元的区室化、轴突长度和高能量需求，线粒体的有效运输被认为对神经元特别重要（[3] 中综述）。然而，这些结果大部分是通过短期体外神经元培养模型获得的，目前对体外或体内哺乳动物中枢神经系统成熟轴突的线粒体动力学知之甚少。此外，最近的证据表明，线粒体固定在轴突上的特定点（例如突触前布顿）在轴突形态发生中发挥着关键作用 [4, 5]。我们报告说，随着皮质轴突的成熟，线粒体（但不是其他货物）的运动性显着降低，这与突触前位点的定位增加相一致。我们还证明，使用光转换，体外成熟的轴突显示出令人惊讶的有限的远程线粒体运输。最后，在麻醉或清醒小鼠中使用体内双光子显微镜，我们首次证明体内远端皮质轴突的线粒体运动性也非常低。这些结果表明，线粒体固定和突触前定位是体外和体内成熟中枢神经系统轴突的重要标志。
The importance of mitochondria for neuronal function is evident by the large number of neurodegenerative diseases that have been associated with a disruption of mitochondrial function or transport (reviewed in [1, 2]). Mitochondria are essential for proper biological function as a result of their ability to produce ATP through oxidative phosphorylation, buffer cytoplasmic calcium, regulate lipid biosynthesis, and trigger apoptosis (reviewed in [2]). Efficient transport of mitochondria is thought to be particularly important in neurons in light of their compartmentalization, length of axonal processes, and high-energy requirements (reviewed in [3]). However, the majority of these results were obtained using short-term, in vitro neuronal culture models, and very little is currently known about mitochondrial dynamics in mature axons of the mammalian CNS in vitro or in vivo. Furthermore, recent evidence has demonstrated that mitochondrial immobilization at specific points along the axon, such as presynaptic boutons, play critical roles in axon morphogenesis [4, 5]. We report that as cortical axons mature, motility of mitochondria (but not other cargoes) is dramatically reduced and this coincides with increased localization to presynaptic sites. We also demonstrate using photo-conversion that in vitro mature axons display surprisingly limited long-range mitochondrial transport. Finally, using in vivo two-photon microscopy in anesthetized or awake-behaving mice, we document for the first time that mitochondrial motility is also remarkably low in distal cortical axons in vivo. These results argue that mitochondrial immobilization and presynaptic localization are important hallmarks of mature CNS axons both in vitro and in vivo.