Dietary Mg²⁺ Intake and the Na⁺/Mg²⁺ Exchanger SLC41A1 Influence Components of Mitochondrial Energetics in Murine Cardiomyocytes

• Main Authors: Zuzana Tatarkova, Jeroen H. F. de Baaij, Marian Grendar, Jörg R. Aschenbach, Peter Racay, Caro Bos, Gerhard Sponder, Joost G. J. Hoenderop, Monika Röntgen, Monika Turcanova Koprusakova, Martin Kolisek
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: International Journal of Molecular Sciences
• Subjects: magnesium; cardiomyocyte; Krebs cycle; electron transport chain; oxidative phosphorylation; Na⁺/Mg²⁺ exchanger
• Online Access: https://www.mdpi.com/1422-0067/21/21/8221

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⁺/Mg²⁺ 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 <i>Slc41a1</i>^−/− mice fed a diet with either normal or low Mg content. Our data demonstrate that both, the type of Mg diet and the <i>Slc41a1</i> genotype largely impact on the activities of enzymes of the Krebs cycle and ETC. Moreover, a compensatory effect of <i>Slc41a1</i>^−/− 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 <i>Slc41a1</i> genotype. Thus, our data delineate the effect of dietary Mg content and of SLC41A1 functionality on the energy-production in cardiac mitochondria.