Department of Physiology and Biophysics, R-430, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
J Bioenerg Biomembr. 2011 Dec;43(6):581-6. doi: 10.1007/s10863-011-9392-1.
Mitochondria contribute to neuronal function not only via their ability to generate ATP, but also via their ability to buffer large Ca(2+) loads. This review summarizes evidence that mitochondrial Ca(2+) sequestration is especially important for sustaining the function of vertebrate motor nerve terminals during repetitive stimulation. Motor terminal mitochondria can sequester large amounts of Ca(2+) because they have mechanisms for limiting both the mitochondrial depolarization and the increase in matrix free [Ca(2+)] associated with Ca(2+) influx. In mice expressing mutations of human superoxide dismutase -1 (SOD1) that cause some cases of familial amyotrophic lateral sclerosis (fALS), motor terminals degenerate well before the death of motor neuron cell bodies. This review presents evidence for early and progressive mitochondrial dysfunction in motor terminals of mutant SOD1 mice (G93A, G85R). This dysfunction would impair mitochondrial ability to sequester stimulation-associated Ca(2+) loads, and thus likely contributes to the early degeneration of motor terminals.
线粒体不仅通过产生 ATP 的能力为神经元功能做出贡献，还通过缓冲大量 Ca(2+)负载的能力做出贡献。这篇综述总结了证据表明，线粒体 Ca(2+)摄取对于维持脊椎动物运动神经末梢在重复刺激期间的功能特别重要。运动终末线粒体可以摄取大量的 Ca(2+)，因为它们具有限制线粒体去极化和与 Ca(2+)内流相关的基质游离 [Ca(2+)]增加的机制。在表达导致某些家族性肌萎缩侧索硬化症 (fALS)的人类超氧化物歧化酶-1 (SOD1)突变的小鼠中，运动终末在运动神经元细胞体死亡之前就已经退化。这篇综述提供了证据表明，突变型 SOD1 小鼠（G93A、G85R）的运动终末存在早期和进行性的线粒体功能障碍。这种功能障碍会损害线粒体摄取与刺激相关的 Ca(2+)负载的能力，因此可能导致运动终末的早期退化。
