Griffiths Elinor J, Rutter Guy A
Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
Biochim Biophys Acta. 2009 Nov;1787(11):1324-33. doi: 10.1016/j.bbabio.2009.01.019. Epub 2009 Feb 3.
Mitochondrial Ca(2+) transport was initially considered important only in buffering of cytosolic Ca(2+) by acting as a "sink" under conditions of Ca(2+) overload. The main regulator of ATP production was considered to be the relative concentrations of high energy phosphates. However, work by Denton and McCormack in the 1970s and 1980s showed that free intramitochondrial Ca(2+) (Ca(2+)) activated dehydrogenase enzymes in mitochondria, leading to increased NADH and hence ATP production. This leads them to propose a scheme, subsequently termed a "parallel activation model" whereby increases in energy demand, such as hormonal stimulation or increased workload in muscle, produced an increase in cytosolic [Ca(2+)] that was relayed by the mitochondrial Ca(2+) transporters into the matrix to give an increase in Ca(2+). This then stimulated energy production to meet the increased energy demand. With the development of methods for measuring Ca(2+) in living cells that proved Ca(2+) changed over a dynamic physiological range rather than simply soaking up excess cytosolic [Ca(2+)], this model has now gained widespread acceptance. However, work by ourselves and others using targeted probes to measure changes in both [Ca(2+)] and [ATP] in different cell compartments has revealed variations in the interrelationships between these two in different tissues, suggesting that metabolic regulation by Ca(2+) is finely tuned to the demands and function of the individual organ.
线粒体钙（Ca²⁺）转运最初仅被认为在钙超载情况下作为“汇”缓冲胞质钙（Ca²⁺）时才重要。ATP生成的主要调节因素被认为是高能磷酸盐的相对浓度。然而，丹顿和麦科马克在20世纪70年代和80年代的研究表明，线粒体内游离钙（[Ca²⁺]m）激活线粒体中的脱氢酶，导致NADH增加，从而使ATP生成增加。这使他们提出了一个后来被称为“平行激活模型”的方案，即能量需求增加，如激素刺激或肌肉工作量增加，会使胞质[Ca²⁺]升高，线粒体钙转运体将其传递到基质中，使[Ca²⁺]m升高。然后这会刺激能量生成以满足增加的能量需求。随着测量活细胞中[Ca²⁺]m的方法的发展，证明[Ca²⁺]m在动态生理范围内变化，而不是简单地吸收过量胞质[Ca²⁺]，该模型现已得到广泛认可。然而，我们和其他人使用靶向探针测量不同细胞区室中[Ca²⁺]和[ATP]变化的研究表明，这两者之间的相互关系在不同组织中存在差异，这表明钙对代谢调节是根据各个器官的需求和功能进行精细调整的。
