Role of mitochondrial Ca2+ in the regulation of cellular energetics.
Role of mitochondrial Ca2+ in the regulation of cellular energetics.
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DOI：
10.1021/bi2018909
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发表时间：
2012-04-10
期刊：
影响因子：
2.9
通讯作者：
Balaban, Robert S.
中科院分区：
文献类型：
--
作者：
Glancy, Brian;Balaban, Robert S.
钙是参与许多细胞功能调节的重要信号分子。 Ca2+ 离子膜梯度中的大自由能使得 Ca2+ 信号传导本质上对可用的细胞自由能（主要以 ATP 形式）敏感。此外，Ca2+ 调节许多细胞 ATP 消耗反应，如肌肉收缩、胞吐作用、生物合成和神经元信号传导。因此，Ca2+ 成为信号分子的合理候选者，可在多种形式的细胞工作变化过程中调节 ATP 水解和合成。线粒体是哺乳动物细胞有氧能量产生的主要来源，并且在内膜上维持较大的 Ca2+ 梯度，为该分子提供信号传导潜力。细胞质和线粒体 [Ca2+] 之间已证实的联系、转运机制的鉴定以及线粒体与 Ca2+ 释放位点的接近程度进一步支持了以下观点：Ca2+ 可以是细胞质与线粒体能量代谢相互作用中的重要信号分子。在这里，我们回顾了线粒体内 Ca2+ 在 ATP 生成调节中发挥作用的位点，并可能有助于细胞代谢稳态的协调。对分离酶的早期研究指出了几种受 Ca2+ 刺激的基质脱氢酶，这在完整的线粒体以及细胞和体内系统中得到了证实。然而，对这些完整系统的研究表明 Ca2+ 对线粒体能量转换具有更广泛的影响。许多监测 NADH、线粒体膜电位、耗氧量和工作负荷的非侵入性方法表明，Ca2+ 对 NADH 生成的其他元件以及氧化磷酸化的下游元件（包括 F1FO-ATP 酶和细胞色素链）有显着影响。线粒体能量转换的 Ca2+ 修饰的这些其他潜在元素将是本综述的重点。尽管大多数具体的分子机制尚未阐明，但很明显，Ca2+ 提供了线粒体能量代谢的平衡激活，这超过了单独脱氢酶的改变。
Calcium is an important signaling molecule involved in the regulation of many cellular functions. The large free energy in the Ca2+ ion membrane gradients make Ca2+ signaling inherently sensitive to the available cellular free energy, primarily in the form of ATP. In addition, Ca2+ regulates many cellular ATP consuming reactions such as muscle contraction, exocytosis, biosynthesis and neuronal signaling. Thus, Ca2+ becomes a logical candidate as a signaling molecule to modulate ATP hydrolysis and synthesis during changes in numerous forms of cellular work. Mitochondria are the primary source of aerobic energy production in mammalian cells and also maintain a large Ca2+ gradient across their inner membrane providing a signaling potential for this molecule. The demonstrated link between cytosolic and mitochondrial [Ca2+], identification of transport mechanisms as well as proximity of mitochondria to Ca2+ release sites further supports the notion that Ca2+ can be an important signaling molecule in the energy metabolism interplay of the cytosol with the mitochondria. Here we review sites within the mitochondria where Ca2+ plays a role in the regulation of ATP generation and potentially contributes to the orchestration of the cellular metabolic homeostasis. Early work on isolated enzymes pointed to several matrix dehydrogenases that are stimulated by Ca2+, which were confirmed in the intact mitochondrion as well as cellular and in vivo systems. However, studies in these intact systems suggested a more expansive influence of Ca2+ on mitochondrial energy conversion. Numerous non-invasive approaches monitoring NADH, mitochondrial membrane potential, oxygen consumption and workloads suggest significant Ca2+ effects on other elements of NADH generation as well as downstream elements of oxidative phosphorylation including the F1FO-ATPase and the cytochrome chain. These other potential elements of Ca2+ modification of mitochondrial energy conversion will be the focus of this review. Though most of specific molecular mechanisms have yet to be elucidated, it is clear that Ca2+ provides a balanced activation of mitochondrial energy metabolism which exceeds the alteration of dehydrogenases alone.
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在具有高能碰撞解离的 LTQ-Orbitrap 上使用 iTRAQ 进行定量线粒体磷酸蛋白质组学。
影响因子：
4.4
作者：
Boja, Emily S.;Phillips, Darci;French, Stephanie A.;Harris, Robert A.;Balaban, Robert S.
通讯作者：
Balaban, Robert S.
影响因子：
64.5
作者：
Cárdenas C;Miller RA;Smith I;Bui T;Molgó J;Müller M;Vais H;Cheung KH;Yang J;Parker I;Thompson CB;Birnbaum MJ;Hallows KR;Foskett JK
通讯作者：
Foskett JK
DOI：
10.1196/annals.1380.013
发表时间：
2006-01-01
期刊：
INTERACTIVE AND INTEGRATIVE CARDIOLOGY
影响因子：
--
作者：
Balaban, Robert S.
通讯作者：
Balaban, Robert S.
影响因子：
--
作者：
BOERTH, RC;COVELL, JW;POOL, PE
通讯作者：
POOL, PE
影响因子：
5
作者：
BEIS, I;NEWSHOLME, EA
通讯作者：
NEWSHOLME, EA