The role of calcium in the regulation of mitochondrial metabolism.
The role of calcium in the regulation of mitochondrial metabolism.
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DOI：
10.1042/bst0080266
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发表时间：
1980-06
影响因子：
3.9
通讯作者：
R. Denton;J. G. Mccormack
中科院分区：
文献类型：
--
作者：
R. Denton;J. G. Mccormack
鱼藤酮和寡霉素的存在（Scott & Nicholls，1980）。这种抑制剂的组合应防止任何Ca+摄取到线粒体基质中。如表1所示，在这些条件下，沉淀的Ca 2+大大减少，而溶解的CaZ+实际上增加。这清楚地表明，突触体CaZ+的大部分位于一个隔室，是响应于线粒体膜电位，因此可以确定与线粒体基质。消除线粒体膜电位的必要性抑制氧化磷酸化。因此，可以认为，颗粒Ca 2+的减少是由于抑制了ATP对Ca 2+依赖性ATP酶的供应，从而在毛地黄皂苷抗性囊泡内积累Ca 2+。然而，糖酵解允许在这些条件下维持显著的ATP浓度（Scott & Nicholls，1980），而单独存在寡霉素（其抑制线粒体ATP合酶而不降低内部线粒体的膜电位（Scott & Nicholls，1980））不会减少沉淀中的Ca 2+（表1）。因此，结论是，线粒体基质代表的主要网站内的Ca 2+的积累，在这些条件下，约85 nmol的Ca 2 +/mg的线粒体蛋白在分离的突触体内。这完全在脑线粒体积累Ca 2+的能力范围内，但足以使efRux途径饱和（Nicholls & Scott，1980）。因此，线粒体在这些条件下调节胞质Ca 2+浓度是可行的。然而，有一个前提条件：突触体的总Ca 2+含量在16分钟时仍在增加（图1），这意味着内部线粒体能够充分降低胞质游离Ca 2+浓度，以施加穿过质膜的净向内Ca 2+通量。因此，这是否代表了一种接近稳态的方法，或者具有缺陷质膜Ca 2 +-eWux通路的突触体的比例是否对观察到的总突触体群体的Ca 2+摄取做出不成比例的贡献，仍有待确定。先前的研究（Kendrick等人，1977; Blaustein等人。1978; Rahamimoff & Abramovitz，1978）强调了突触体内网状膜ATP依赖性Ca*+积累的作用。然而，本研究表明，线粒体，其精心设计的Ca 2+调节机制，发挥主要作用内的细胞质的分离的突触体。
presence of rotenone and oligomycin (Scott & Nicholls, 1980). This combination of inhibitors should prevent any Ca’+ uptake into the matrices of the mitochondria. As is shown in Table 1, the pelleted Ca2+ was greatly diminished under these conditions, whereas the solubilized CaZ+ actually increases. This clearly indicates that the major proportion of the synaptosomal CaZ+ is located in a compartment that is responsive to the mitochondrial membrane potential, and can therefore be identified with the mitochondrial matrix. Abolition of the mitochondrial membrane potential of necessity inhibits oxidative phosphorylation. Thus it could be argued that the diminished pellet Ca2+ resulted from the inhibition of the ATP supply to a Ca2+dependent ATPase accumulating Ca2+ within digitonin-resistant vesicles. However glycolysis allows significant ATP concentrations to be maintained under these conditions (Scott & Nicholls, 1980), whereas the presence of oligomycin alone, which inhibits the mitochondrial ATP synthase without lowering the membrane potential of the internal mitochondria (Scott & Nicholls, 1980), does not diminish the Ca2+ in the pellet (Table 1). The conclusion is therefore that the mitochondrial matrix represents the major site of Ca2+ accumulation within isolated synaptosomes amounting to some 85nmol of Ca2+/mg of mitochondrial protein under these conditions. This is well within the capacity of brain mitochondria to accumulate Ca2+, but is sufficient to saturate the efRux pathway (Nicholls & Scott, 1980). It is therefore feasible that the mitochondria regulate cytosolic Ca2+ concentrations under these conditions. There is, however, one proviso to make: the total Ca2+ content of the synaptosome is still increasing at 16min (Fig. l), implying that the internal mitochondria are capable of decreasing the cytosolic free Ca2+ concentration sufficiently to impose a net inward Ca2+ flux across the plasma membrane. It remains to be established therefore whether this represents an approach towards a steady-state, or whether a proportion of synaptosomes with a defective plasma membrane Ca2+-eWux pathway contributes disproportionately to the observed Ca2+ uptake by the total synaptosomal population. Previous studies (Kendrick et al., 1977; Blaustein et al.. 1978; Rahamimoff & Abramovitz, 1978) emphasized the role of ATP-dependent Ca*+ accumulation by intra-synaptosomal reticular membranes. However, the present study demonstrates that the mitochondria, with their elaborate Ca2+-regulatory mechanism, play the predominant role within the cytosol of the isolated synaptosome.