The distinct roles of calcium in rapid control of neuronal glycolysis and the tricarboxylic acid cycle.
The distinct roles of calcium in rapid control of neuronal glycolysis and the tricarboxylic acid cycle.
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DOI：
10.7554/elife.64821
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发表时间：
2021-02-08
期刊：
影响因子：
7.7
通讯作者：
Yellen G
中科院分区：
文献类型：
--
作者：
Díaz-García CM;Meyer DJ;Nathwani N;Rahman M;Martínez-François JR;Yellen G
当神经元处于强烈的活动期时，能量需求的随之增加可以通过糖酵解、三羧酸（TCA）循环和氧化磷酸化的协调激活来满足。然而，糖酵解激活的触发因素是未知的，并且Ca 2+在线粒体反应中的作用一直存在争议。在急性海马切片中使用遗传编码的荧光生物传感器和NAD（P）H自发荧光成像，在这里，我们发现线粒体中的Ca 2+摄取负责线粒体NADH的积累，可能通过Ca 2+激活TCA循环中的脱氢酶。在胞质溶胶中，我们没有观察到Ca 2 +/钙调蛋白信号通路或AMPK在急性刺激下介导糖酵解NADH升高中的作用。神经元中的有氧糖酵解主要由Na+或Ca 2+挤出引起的能量需求触发，并且在小鼠齿状颗粒细胞中，Ca 2+产生了大部分这种需求。
When neurons engage in intense periods of activity, the consequent increase in energy demand can be met by the coordinated activation of glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. However, the trigger for glycolytic activation is unknown and the role for Ca2+ in the mitochondrial responses has been debated. Using genetically encoded fluorescent biosensors and NAD(P)H autofluorescence imaging in acute hippocampal slices, here we find that Ca2+ uptake into the mitochondria is responsible for the buildup of mitochondrial NADH, probably through Ca2+ activation of dehydrogenases in the TCA cycle. In the cytosol, we do not observe a role for the Ca2+/calmodulin signaling pathway, or AMPK, in mediating the rise in glycolytic NADH in response to acute stimulation. Aerobic glycolysis in neurons is triggered mainly by the energy demand resulting from either Na+ or Ca2+ extrusion, and in mouse dentate granule cells, Ca2+ creates the majority of this demand.