Flippo Kyle H, Strack Stefan
Department of Pharmacology, University of Iowa, Iowa City, USA.
Department of Pharmacology, University of Iowa, Iowa City, USA
J Cell Sci. 2017 Feb 15;130(4):671-681. doi: 10.1242/jcs.171017. Epub 2017 Feb 2.
Mitochondria fulfill numerous cellular functions including ATP production, Ca buffering, neurotransmitter synthesis and degradation, ROS production and sequestration, apoptosis and intermediate metabolism. Mitochondrial dynamics, a collective term for the processes of mitochondrial fission, fusion and transport, governs mitochondrial function and localization within the cell. Correct balance of mitochondrial dynamics is especially important in neurons as mutations in fission and fusion enzymes cause peripheral neuropathies and impaired development of the nervous system in humans. Regulation of mitochondrial dynamics is partly accomplished through post-translational modification of mitochondrial fission and fusion enzymes, in turn influencing mitochondrial bioenergetics and transport. The importance of post-translational regulation is highlighted by numerous neurodegenerative disorders associated with post-translational modification of the mitochondrial fission enzyme Drp1. Not surprisingly, mitochondrial dynamics also play an important physiological role in the development of the nervous system and synaptic plasticity. Here, we highlight recent findings underlying the mechanisms and regulation of mitochondrial dynamics in relation to neurological disease, as well as the development and plasticity of the nervous system.
线粒体履行多种细胞功能,包括三磷酸腺苷(ATP)生成、钙缓冲、神经递质合成与降解、活性氧(ROS)生成与隔离、细胞凋亡及中间代谢。线粒体动力学是线粒体分裂、融合及运输过程的统称,它控制着线粒体在细胞内的功能及定位。线粒体动力学的正确平衡在神经元中尤为重要,因为裂变和融合酶的突变会导致人类周围神经病变及神经系统发育受损。线粒体动力学的调节部分是通过对线粒体裂变和融合酶进行翻译后修饰来实现的,进而影响线粒体生物能量学及运输。与线粒体裂变酶动力相关蛋白1(Drp1)的翻译后修饰有关的众多神经退行性疾病凸显了翻译后调节的重要性。不出所料,线粒体动力学在神经系统发育及突触可塑性中也发挥着重要的生理作用。在此,我们着重介绍了与神经疾病以及神经系统发育和可塑性相关的线粒体动力学机制及调节的最新研究发现。