DECODING OF CYTOSOLIC CALCIUM OSCILLATIONS IN THE MITOCHONDRIA
DECODING OF CYTOSOLIC CALCIUM OSCILLATIONS IN THE MITOCHONDRIA
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DOI：
10.1016/0092-8674(95)90430-1
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发表时间：
1995-08-11
期刊：
影响因子：
64.5
通讯作者：
THOMAS, AP
中科院分区：
文献类型：
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作者：
HAJNOCZKY, G;ROBBGASPERS, LD;THOMAS, AP
胞质Ca 2+（[Ca 2 +]（c））的频率调制振荡被认为在信号转导中是重要的，但是很难将[Ca 2 +]（c）振荡与Ca 2+调节的靶点的活性直接关联。我们通过同时监测单个肝细胞中线粒体Ca ~（2+）（[Ca ~（2+）]（m））和黄素蛋白和吡啶核苷酸的氧化还原状态以及[Ca ~（2+）]（c）来研究Ca ~（2+）敏感性线粒体脱氢酶（CSMDHs）的调控。IP 3依赖性激素诱导的[Ca ~（2+）]（c）振荡以[Ca ~（2+）]（m）振荡的形式有效地传递到线粒体。每个[Ca 2 +]（m）尖峰足以引起CSMDH的最大瞬时激活，并且频率高于0.5/min的[Ca 2 +]（m）振荡引起线粒体代谢的持续激活。相比之下，持续的[Ca 2 +]（c）增加仅产生短暂的CSMDH激活，缓慢或部分[Ca 2 +]（c）升高对增加[Ca 2 +]（m）或刺激CSMDH无效。我们的结论是，线粒体被调谐到振荡[Ca 2 +]（c）信号，其频率可以控制CSMDHs在整个范围内的潜在活动。
Frequency-modulated oscillations of cytosolic Ca2+ ([Ca2+](c)) are believed to be important in signal transduction, but it has been difficult to correlate [Ca2+](c) oscillations directly with the activity of Ca2+-regulated targets. We have studied the control of Ca2+-sensitive mitochondrial dehydrogenases (CSMDHs) by monitoring mitochondrial Ca2+ ([Ca2+](m)) and the redox state of flavoproteins and pyridine nucleotides simultaneously with [Ca2+](c) in single hepatocytes. Oscillations of [Ca2+](c) induced by IP3-dependent hormones were efficiently transmitted to the mitochondria as [Ca2+](m) oscillations. Each [Ca2+](m) spike was sufficient to cause a maximal transient activation of the CSMDHs and [Ca2+](m) oscillations at frequencies above 0.5 per minute caused a sustained activation of mitochondrial metabolism. By contrast, sustained [Ca2+](c) increases yielded only transient CSMDH activation, and slow or partial [Ca2+](c) elevations were ineffective in increasing [Ca2+](m) or stimulating CSMDHs. We conclude that the mitochondria are tuned to oscillating [Ca2+](c) signals, the frequency of which can control the CSMDHs over the full range of potential activities.