神经活动和钙/钙调蛋白依赖性蛋白激酶II保护衰老秀丽隐杆线虫神经元中的线粒体免于碎片化。
Neural activity and CaMKII protect mitochondria from fragmentation in aging Caenorhabditis elegans neurons.
作者信息
Jiang Hao-Ching, Hsu Jiun-Min, Yen Chien-Ping, Chao Chi-Chao, Chen Ruey-Hwa, Pan Chun-Liang
机构信息
Institute of Molecular Medicine, National Taiwan University, 10002 Taipei, Taiwan;
Department of Neurology, National Taiwan University Hospital, 10002 Taipei, Taiwan;
出版信息
Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):8768-73. doi: 10.1073/pnas.1501831112. Epub 2015 Jun 29.
Decline in mitochondrial morphology and function is a hallmark of neuronal aging. Here we report that progressive mitochondrial fragmentation is a common manifestation of aging Caenorhabditis elegans neurons and body wall muscles. We show that sensory-evoked activity was essential for maintaining neuronal mitochondrial morphology, and this activity-dependent mechanism required the Degenerin/ENaC sodium channel MEC-4, the L-type voltage-gated calcium channel EGL-19, and the Ca/calmodulin-dependent kinase II (CaMKII) UNC-43. Importantly, UNC-43 phosphorylated and inhibited the dynamin-related protein (DRP)-1, which was responsible for excessive mitochondrial fragmentation in neurons that lacked sensory-evoked activity. Moreover, enhanced activity in the aged neurons ameliorated mitochondrial fragmentation. These findings provide a detailed description of mitochondrial behavior in aging neurons and identify activity-dependent DRP-1 phosphorylation by CaMKII as a key mechanism in neuronal mitochondrial maintenance.
线粒体形态和功能的衰退是神经元衰老的一个标志。在此，我们报告渐进性线粒体碎片化是衰老的秀丽隐杆线虫神经元和体壁肌肉的常见表现。我们表明，感觉诱发活动对于维持神经元线粒体形态至关重要，并且这种活动依赖性机制需要退化素/上皮钠通道MEC-4、L型电压门控钙通道EGL-19以及钙/钙调蛋白依赖性激酶II（CaMKII）UNC-43。重要的是，UNC-43磷酸化并抑制了动力相关蛋白（DRP）-1，DRP-1导致缺乏感觉诱发活动的神经元中过度的线粒体碎片化。此外，衰老神经元中增强的活动改善了线粒体碎片化。这些发现详细描述了衰老神经元中线粒体的行为，并确定CaMKII介导的活动依赖性DRP-1磷酸化是神经元线粒体维持的关键机制。
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