Cytosolic Ca2+ regulates the energization of isolated brain mitochondria by formation of pyruvate through the malate-aspartate shuttle
Cytosolic Ca2+ regulates the energization of isolated brain mitochondria by formation of pyruvate through the malate-aspartate shuttle
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DOI：
10.1042/bj20110765
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发表时间：
2012-05-01
影响因子：
4.1
通讯作者：
Striggow, Frank
中科院分区：
文献类型：
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作者：
Gellerich, Frank Norbert;Gizatullina, Zemfira;Striggow, Frank
分离的脑线粒体的谷氨酸依赖性呼吸受胞浆Ca~(2+)(S-0.5=225+/-22 nM)调节。我们现在还证明了α-甘油磷酸依赖的呼吸是由Ca-Cyt(2+)控制的(S-0.5=60+/-10 nM)。在较高的Ca-Cyt(2+)(>；600 nM)条件下，BM积累了钙离子，从而提高了线粒体内脱氢酶的速率。Ca~(2+)诱导的态3呼吸增量随底物的增加而递减，顺序为glutamate>；alpha-oxoglutarate>；isocitrate>；alpha-glycerophosphate>；pyruvate.而丙酮酸的氧化只受Ca-Cyt(2+)的影响很小，而丙酮酸的形成受Ca-Cyt(2+)的严格控制。乳酸脱氢酶(LDH)通过其共同底物对NADH/NAD(+)与苹果酸-天冬氨酸穿梭(MAS)相连，以Aralar为中心组分。在由BM、胞浆酶MAS和LDH组成的重组系统中，Ca-Cyt(2+)的增加导致OXPHOS(氧化磷酸化)速率最多增加5倍，这是由于底物供应的增加，其作用类似于“油门踏板”。相反，Ca-MIT(2+)(线粒体内的钙离子)调节线粒体基质中底物的氧化速率。我们推测，Ca-Cyt(2+)是调节线粒体能量以适应完整神经元需求的关键因素。
The glutamate-dependent respiration of isolated BM (brain mitochondria) is regulated by Ca-cyt(2+) (cytosolic Ca2+) (S-0.5 = 225 +/- 22 nM) through its effects on aralar. We now also demonstrate that the a-glycerophosphate-dependent respiration is controlled by Ca-cyt(2+) (S-0.5 = 60 +/- 10 nM). At higher Ca-cyt(2+) (>600 nM), BM accumulate Ca2+ which enhances the rate of intramitochondrial dehydrogenases. The Ca2+-induced increments of state 3 respiration decrease with substrate in the order glutamate>alpha-oxoglutarate>isocitrate>alpha-glycerophosphate>pyruvate. Whereas the oxidation of pyruvate is only slightly influenced by Ca-cyt(2+), we show that the formation of pyruvate is tightly controlled by Ca-cyt(2+). Through its common substrate couple NADH/NAD(+), the formation of pyruvate by LDH (lactate dehydrogenase) is linked to the MAS (malate-aspartate shuttle) with aralar as a central component. A rise in Ca-cyt(2+) in a reconstituted system consisting of BM, cytosolic enzymes of MAS and LDH causes an up to 5-fold enhancement of OXPHOS (oxidative phosphorylation) rates that is due to an increased substrate supply, acting in a manner similar to a 'gas pedal'. In contrast, Ca-mit(2+) (intramitochondrial Ca2+) regulates the oxidation rates of substrates which are present within the mitochondrial matrix. We postulate that Ca-cyt(2+) is a key factor in adjusting the mitochondrial energization to the requirements of intact neurons.