Abstract
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 Slc41a1−/− mice fed a diet with either normal or low Mg content. Our data demonstrate that both, the type of Mg diet and the Slc41a1 genotype largely impact on the activities of enzymes of the Krebs cycle and ETC. Moreover, a compensatory effect of Slc41a1−/− 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 Slc41a1 genotype. Thus, our data delineate the effect of dietary Mg content and of SLC41A1 functionality on the energy-production in cardiac mitochondria.
Highlights
Cardiovascular diseases (CVD) account for ~31% of all estimated deaths worldwide
We have examined whether the presence or absence of functional SLC41A1, influences the enzymatic activities of the key components of the Krebs cycle (ACON, isocitrate dehydrogenase (ICDH), and ketoglutarate dehydrogenase (KGDH)) and/or activities of the complexes of electron transport chain (ETC) (CI–CIV) including F1Fo-ATPase (CV) in mitochondria of cells from murine hearts
Dietary Mg depletion quenched the activity of Krebs cycle components (ACON, ICDH and KGDH), and production of ETC substrates
Summary
Cardiovascular diseases (CVD) account for ~31% of all estimated deaths worldwide (www.who.int). Ageing per se is the major intrinsic risk factor for heart failure and CVD [1]. An unhealthy diet including excessive food intake, alcohol consumption, smoking, low physical activity, and stress have been identified as the most prominent among known extrinsic risk factors for CVD. The typical Western diet, which is rich in processed food with high sugar and fat content, lacks sufficient amounts of Mg [8,9]. This can lead to subclinical intracellular Mg deficiency, which is rarely diagnosed [9,10]. Chronic Mg deficiency imposes a serious problem, leading to health complications including CVD [9,11]
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