Iron-dependent changes in cellular energy metabolism: influence on citric acid cycle and oxidative phosphorylation
Iron-dependent changes in cellular energy metabolism: influence on citric acid cycle and oxidative phosphorylation
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DOI：
10.1016/s0005-2728(99)00088-2
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发表时间：
1999-11-10
影响因子：
4.3
通讯作者：
Weiss, G
中科院分区：
文献类型：
--
作者：
Oexle, H;Gnaiger, E;Weiss, G
铁通过一种涉及铁调节蛋白的翻译机制来调节关键的柠檬酸循环酶乌头酸酶的表达。因此，本研究旨在研究铁干扰对人类细胞系K-562柠檬酸循环活性、氧化磷酸化和线粒体呼吸的影响。与以前的数据一致，铁增加了线粒体乌头酸酶的活性，而加入铁螯合剂去铁胺(DFO)后，它的活性降低了。有趣的是，铁还对其他三种柠檬酸循环酶，即柠檬酸合成酶、异柠檬酸脱氢酶和琥珀酸脱氢酶有正向影响，而DFO会降低这些酶的活性。因此，补充铁导致柠檬酸循环中还原当量(NADH)的形成增加，从而增加线粒体的氧耗，并通过氧化磷酸化形成ATP，如本文所示。这反过来又会导致葡萄糖利用的下调。相反，当铁缺乏时，所有这些代谢途径都会减少，因此糖酵解和乳酸形成显著增加，以补偿在DFO存在下通过氧化磷酸化减少的ATP产量。我们的结果指出，在人类细胞中，铁稳态、氧气供应和细胞能量代谢之间存在复杂的相互作用。(C)1999 Elsevier Science B.V.保留所有权利。
Iron modulates the expression of the critical citric acid cycle enzyme aconitase via a translational mechanism involving iron regulatory proteins. Thus, the present study was undertaken to investigate the consequences of iron perturbation on citric acid cycle activity, oxidative phosphorylation and mitochondrial respiration in the human cell line K-562. In agreement with previous data iron increases the activity of mitochondrial aconitase while it is reduced upon addition of the iron chelator desferrioxamine (DFO). Interestingly, iron also positively affects three other citric acid cycle enzymes, namely citrate synthase, isocitric dehydrogenase, and succinate dehydrogenase, while DFO decreases the activity of these enzymes. Consequently, iron supplementation results in increased formation of reducing equivalents (NADH) by the citric acid cycle, and thus in increased mitochondrial oxygen consumption and ATP formation via oxidative phosphorylation as shown herein. This in turn leads to downregulation of glucose utilization. In contrast, all these metabolic pathways are reduced upon iron depletion, and thus glycolysis and lactate formation are significantly increased in order to compensate for the decrease in ATP production via oxidative phosphorylation in the presence of DFO. Our results point to a complex interaction between iron homeostasis, oxygen supply and cellular energy metabolism in human cells. (C) 1999 Elsevier Science B.V. All rights reserved.