Nicholls David G, Vesce Sabino, Kirk Liana, Chalmers Susan
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Cell Calcium. 2003 Oct-Nov;34(4-5):407-24. doi: 10.1016/s0143-4160(03)00144-1.
The mitochondrion has moved to the center stage in the drama of the life and death of the neuron. The mitochondrial membrane potential controls the ability of the organelle to generate ATP, generate reactive oxygen species and sequester Ca(2+) entering the cell. Each of these processes interact, and their deconvolution is far from trivial. The cultured cerebellar granule cell provides a model in which knowledge gained from studies on isolated mitochondria can be applied to study the role played by the organelles in the maintenance of Ca(2+) homeostasis in the cell under resting, stimulated and pathophysiological conditions. In particular, mitochondria play a complex role in the response of the neuron to excitotoxic stimulation of NMDA and AMPA-kainate selective glutamate receptors. One goal of research in this area is to provide clues as to possible ways in which modulators of mitochondrial function may be used as neuroprotective agents, since mitochondrial Ca(2+) accumulation seems to play a key role in glutamate excitotoxicity.
线粒体已在神经元生死的“戏剧”中登上了中心舞台。线粒体膜电位控制着该细胞器产生ATP、产生活性氧以及隔离进入细胞的Ca(2+)的能力。这些过程相互作用，而对它们进行剖析绝非易事。培养的小脑颗粒细胞提供了一个模型，在这个模型中，从对分离线粒体的研究中获得的知识可用于研究这些细胞器在静息、刺激和病理生理条件下维持细胞内Ca(2+)稳态中所起的作用。特别是，线粒体在神经元对NMDA和AMPA-海人藻酸选择性谷氨酸受体的兴奋性毒性刺激的反应中发挥着复杂的作用。该领域研究的一个目标是提供线索，以探寻线粒体功能调节剂可能用作神经保护剂的潜在方式，因为线粒体Ca(2+)积累似乎在谷氨酸兴奋性毒性中起关键作用。
