Hormonal Regulation of Intramitochondrial Ca2+ and Oxidative Metabolism in Mammalian Tissues
In mammalian cells, many of the hormones which stimulate energy-requiring processes such as contraction or secretion do so by causing increases in the cytoplasmic concentration of Ca2+ (1). The increased supply of ATP which is thus required is achieved by a concomitant stimulation of oxidative metabolism by the hormones (2). However, in many of these instances there appear to be little or no decreases or even increases in the cellular ATP/ADP and NADH/NAD+ concentration ratios, and therefore this raises the question as to how these increases in oxidative metabolism are achieved. This article will review some of the growing evidence which suggests that at least a part of the mechanism may involve an increase in the concentration of Ca2+ in the mitochondrial matrix and the resultant activation of three key Ca2+-sensitive intramitochondrial dehydrogenases. All of these enzymes produce NADH and it is argued that this increased NADH production may be an important means whereby cells can increase oxidative metabolism yet maintain high ATP/ADP ratios. Another important consequence arising from such a scheme is that it suggests that the primary function of the Ca2+ -transport system of the mitochondrial inner membrane under normal physiological conditions in mammalian cells is to relay changes in cytoplasmic Ca2+ concentrations into the mitochondrial matrix and, hence, to control the concentration of Ca2+ in this compartment rather than to buffer or set cytoplasmic Ca2+ concentrations as suggested by others (see 3,4).
KeywordsOxidative Metabolism Mitochondrial Matrix Sensitive Property Cytoplasmic Concentration United Kingdom Introduction
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