Principles of the mitochondrial fusion and fission cycle in neurons
Principles of the mitochondrial fusion and fission cycle in neurons
复制标题
DOI：
10.1242/jcs.118844
复制
发表时间：
2013-05-15
影响因子：
4
通讯作者：
Kaasik, Allen
中科院分区：
文献类型：
--
作者：
Cagalinec, Michal;Safiulina, Dzhamilja;Kaasik, Allen
线粒体融合-裂变动力学在许多重要的细胞过程中发挥着至关重要的作用。这些动力学控制线粒体形态，这反过来又影响几个重要的线粒体特性，包括线粒体生物能量学和质量控制，它们似乎在几种神经退行性疾病中受到影响。然而，一个完整的和定量的了解如何融合裂变动力学控制线粒体形态尚未被描述。在这里，我们利用现代可视化技术提供了一个清晰的解释，融合和裂变如何与线粒体长度和运动神经元。我们的主要发现表明：（1）单个线粒体分裂的概率由其长度决定;（2）单个线粒体融合的概率主要由其运动性决定;（3）线粒体长度的变化驱动融合和分裂周期，偏离该周期可作为避免极端线粒体长度的校正机制;（4）过表达120 Q Htt或Tau的神经元中受损的线粒体运动抑制线粒体融合并导致线粒体缩短，而通过过表达Miro-1刺激线粒体运动恢复线粒体融合速率和大小。总之，我们的研究结果提供了一个新的见解复杂的串扰之间的线粒体动力学的不同过程。这些知识将增加对细胞中动态线粒体功能的理解，特别是与神经退行性疾病相关的神经退行性疾病的发病机制。
Mitochondrial fusion-fission dynamics play a crucial role in many important cell processes. These dynamics control mitochondrial morphology, which in turn influences several important mitochondrial properties including mitochondrial bioenergetics and quality control, and they appear to be affected in several neurodegenerative diseases. However, an integrated and quantitative understanding of how fusion-fission dynamics control mitochondrial morphology has not yet been described. Here, we took advantage of modern visualisation techniques to provide a clear explanation of how fusion and fission correlate with mitochondrial length and motility in neurons. Our main findings demonstrate that: (1) the probability of a single mitochondrion splitting is determined by its length; (2) the probability of a single mitochondrion fusing is determined primarily by its motility; (3) the fusion and fission cycle is driven by changes in mitochondrial length and deviations from this cycle serves as a corrective mechanism to avoid extreme mitochondrial length; (4) impaired mitochondrial motility in neurons overexpressing 120Q Htt or Tau suppresses mitochondrial fusion and leads to mitochondrial shortening whereas stimulation of mitochondrial motility by overexpressing Miro-1 restores mitochondrial fusion rates and sizes. Taken together, our results provide a novel insight into the complex crosstalk between different processes involved in mitochondrial dynamics. This knowledge will increase understanding of the dynamic mitochondrial functions in cells and in particular, the pathogenesis of mitochondrial-related neurodegenerative diseases.