The rapid mode of calcium uptake into heart mitochondria (RaM): comparison to RaM in liver mitochondria
The rapid mode of calcium uptake into heart mitochondria (RaM): comparison to RaM in liver mitochondria
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DOI：
10.1016/s0005-2728(00)00254-1
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发表时间：
2001-04-02
影响因子：
4.3
通讯作者：
Gunter, TE
中科院分区：
文献类型：
--
作者：
Buntinas, L;Gunter, KK;Gunter, TE
先前已经在肝线粒体中鉴定了能够从胞质Ca 2+脉冲中螯合显著量的Ca 2+的Ca 2+摄取机制。这种机制，即Ca 2+摄取的快速模式（RaM），显示在序列中的每个脉冲开始时非常快速地螯合Ca 2 +[Sparagna等（1995）J. Biol. Chem. 270，27510-27515]。然而，心脏线粒体中RaM的存在和性质是未知的，这是本研究的基础。我们发现，心肌线粒体中的RaM功能与肝脏中的RaM的一些特征，但其激活和抑制是完全不同的。这些差异可能代表这两种组织的不同生理适应。在这两种组织中，RaM在Ca 2+脉冲开始时是高度导电的，但被脉冲本身的上升[Ca 2 +]抑制。在心脏线粒体中，在低[Ca 2 +]下通过RaM重建高Ca 2+电导率所需的时间，即RaM的“重置时间”比肝脏中长得多。肝线粒体中的RaM被精胺强烈激活，被ATP或GTP激活，而不受ADP和AMP的影响。在心脏中，RaM被精胺激活的强度要小得多，并且不受ATP或GTP的影响。心脏中的RaM被AMP强烈抑制，并且对ADP具有双相反应，其在低浓度下被激活，在高浓度下被抑制。最后，提出了一个与肝脏和心脏的数据和特征相一致的假设，以解释RaM如何控制每个组织中氧化磷酸化的速率。在这种假设下，RaM的功能是在线粒体内产生短暂的高游离Ca 2+浓度，这可能会激活线粒体内代谢反应，而相对少量的Ca 2+摄取。这一假说与线粒体内[Ca ~（2+）]可用于控制ADP磷酸化速率从而降低Ca ~（2+）诱导的线粒体膜通透性转换（MPT）激活概率的观点一致。(C)2001爱思唯尔科技有限公司。保留所有权利。
A mechanism of Ca2+ uptake, capable of sequestering significant amounts of Ca2+ from cytosolic Ca2+ pulses, has previously been identified in liver mitochondria. This mechanism, the Rapid Mode of Ca2+ uptake (RaM), was shown to sequester Ca2+ very rapidly at the beginning of each pulse in a sequence [Sparagna et al. (1995) J. Biol. Chem. 270, 27510-27515]. The existence and properties of RaM in heart mitochondria, however, are unknown and are the basis for this study. We show that RaM functions in heart mitochondria with some of the characteristics of RaM in liver, but its activation and inhibition are quite different. It is feasible that these differences represent different physiological adaptations in these two tissues. In both tissues, RaM is highly conductive at the beginning of a Ca2+ pulse, but is inhibited by the rising [Ca2+] of the pulse itself. In heart mitochondria, the time required at low [Ca2+] to reestablish high Ca2+ conductivity via RaM i.e, the 'resetting time' of RaM is much longer than in liver. RaM in liver mitochondria is strongly activated by spermine, activated by ATP or GTP and unaffected by ADP and AMP. In heart, RaM is activated much less strongly by spermine and unaffected by ATP or GTP. RaM in heart is strongly inhibited by AMP and has a biphasic response to ADP; it is activated at low concentrations and inhibited at high concentrations. Finally, an hypothesis consistent with the data and characteristics of liver and heart is presented to explain how RaM may function to control the rate of oxidative phosphorylation in each tissue. Under this hypothesis, RaM functions to create a brief, high free Ca2+ concentration inside mitochondria which may activate intramitochondrial metabolic reactions with relatively small amounts of Ca2+ uptake. This hypothesis is consistent with the view that intramitochondrial [Ca2+] may be used to control the rate of ADP phosphorylation in such a way as to rmnlrmze the probability of activating the Ca2+-induced mitochondrial membrane permeability transition (MPT). (C) 2001 Elsevier Science B.V. All rights reserved.