Mitochondrial Mg2+ homeostasis decides cellular energy metabolism and vulnerability to stress

Abstract

Cellular energy production processes are composed of many Mg2+ dependent enzymatic reactions. In fact, dysregulation of Mg2+ homeostasis is involved in various cellular malfunctions and diseases. Recently, mitochondria, energy-producing organelles, have been known as major intracellular Mg2+ stores. Several biological stimuli alter mitochondrial Mg2+ concentration by intracellular redistribution. However, in living cells, whether mitochondrial Mg2+ alteration affect cellular energy metabolism remains unclear. Mg2+ transporter of mitochondrial inner membrane MRS2 is an essential component of mitochondrial Mg2+ uptake system. Here, we comprehensively analyzed intracellular Mg2+ levels and energy metabolism in Mrs2 knockdown (KD) cells using fluorescence imaging and metabolome analysis. Dysregulation of mitochondrial Mg2+ homeostasis disrupted ATP production via shift of mitochondrial energy metabolism and morphology. Moreover, Mrs2 KD sensitized cellular tolerance against cellular stress. These results indicate regulation of mitochondrial Mg2+ via MRS2 critically decides cellular energy status and cell vulnerability via regulation of mitochondrial Mg2+ level in response to physiological stimuli.

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Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence

“…Magnesium acts also as a regulator of the activity of several enzymes of the citric acid cycle, including the isocitrate dehydrogenase and the oxoglutarate dehydrogenase complex (Figure 1, part B) [55]. Furthermore, ATP binds to magnesium ions to compose biologically functional forms and, in the mitochondria, ATP-Mg complexes help export mitochondrial ATP into cytosol and thus deliver energy within the cell [56][57][58].…”

Telomere Homeostasis: Interplay with Magnesium

“…In a manner analogous to the regulation of calcium biochemistry, release or uptake of Mg 2+ can cause large local shifts in [Mg 2+ ], which in turn can regulate a variety of processes, including the regulation of flow of metabolites through glycolysis, the TCA cycle, oxidative phosphorylation, and ATP export from the mitochondria [38]. Critically, Mg 2+ plays a role in telomere maintenance and the activity of telomerase [39].…”