Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4D, 036 01 Martin, Slovakia.
Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500HB Nijmegen, The Netherlands.
Int J Mol Sci. 2020 Nov 3;21(21):8221. doi: 10.3390/ijms21218221.
Cardiomyocytes are among the most energy-intensive cell types. Interplay between the components of cellular magnesium (Mg) homeostasis and energy metabolism in cardiomyocytes is poorly understood. We have investigated the effects of dietary Mg content and presence/functionality of the Na/Mg exchanger SLC41A1 on enzymatic functions of selected constituents of the Krebs cycle and complexes of the electron transport chain (ETC). The activities of aconitate hydratase (ACON), isocitrate dehydrogenase (ICDH), α-ketoglutarate dehydrogenase (KGDH), and ETC complexes CI-CV have been determined in vitro in mitochondria isolated from hearts of wild-type (WT) and mice fed a diet with either normal or low Mg content. Our data demonstrate that both, the type of Mg diet and the genotype largely impact on the activities of enzymes of the Krebs cycle and ETC. Moreover, a compensatory effect of genotype on the effect of low Mg diet on activities of the tested Krebs cycle enzymes has been identified. A machine-learning analysis identified activities of ICDH, CI, CIV, and CV as common predictors of the type of Mg diet and of CII as suitable predictor of genotype. Thus, our data delineate the effect of dietary Mg content and of SLC41A1 functionality on the energy-production in cardiac mitochondria.
心肌细胞是能量需求最高的细胞类型之一。细胞内镁(Mg)稳态的组成部分与心肌细胞能量代谢之间的相互作用还了解甚少。我们研究了饮食中 Mg 含量以及 Na/Mg 交换蛋白 SLC41A1 的存在/功能对三羧酸循环(Krebs 循环)和电子传递链(ETC)复合物中某些成分的酶功能的影响。通过在体外分离来自野生型(WT)和 小鼠心脏的线粒体,测定了乌头酸水合酶(ACON)、异柠檬酸脱氢酶(ICDH)、α-酮戊二酸脱氢酶(KGDH)和 ETC 复合物 CI-CV 的活性,这些小鼠分别喂食正常或低 Mg 含量的饮食。我们的数据表明,Mg 饮食的类型和 基因型都对 Krebs 循环和 ETC 酶的活性有很大的影响。此外,还发现了 基因型对低 Mg 饮食对测试的 Krebs 循环酶活性的影响的代偿效应。机器学习分析确定了 ICDH、CI、CIV 和 CV 的活性作为 Mg 饮食类型的共同预测因子,而 CII 作为 基因型的合适预测因子。因此,我们的数据描绘了饮食中 Mg 含量和 SLC41A1 功能对心脏线粒体能量产生的影响。