Mitochondria are intracellular magnesium stores: investigation by simultaneous fluorescent imagings in PC12 cells

Abstract

To determine the nature of intracellular Mg2+ stores and Mg2+ release mechanisms in differentiated PC12 cells, Mg2+ and Ca2+ mobilizations were measured simultaneously in living cells with KMG-104, a fluorescent Mg2+ indicator, and fura-2, respectively. Treatment with the mitochondrial uncoupler, carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), increased both the intracellular Mg2+ concentration ([Mg2+]i) and the [Ca2+]i in these cells. Possible candidates as intracellular Mg2+ stores under these conditions include intracellular divalent cation binding sites, endoplasmic reticulum (ER), Mg-ATP and mitochondria. Given that no change in [Mg2+]i was induced by caffeine application, intracellular IP3 or Ca2+ liberated by photolysis, it appears that no Mg2+ release mechanism thus exists that is mediated via the action of Ca2+ on membrane-bound receptors in the ER or via the offloading of Mg2+ from binding sites as a result of the increased [Ca2+]i. FCCP treatment for 2 min did not alter the intracellular ATP content, indicating that Mg2+ was not released from Mg-ATP, at least in the first 2 min following exposure to FCCP. FCCP-induced [Mg2+]i increase was observed at mitochondria localized area, and vice versa. These results suggest that the mitochondria serve as the intracellular Mg2+ store in PC12 cell. Simultaneous measurements of [Ca2+]i and mitochondrial membrane potential, and also of [Ca2+]i and [Mg2+]i, revealed that the initial rise in [Mg2+]i followed that of mitochondrial depolarization for several seconds. These findings show that the source of Mg2+ in the FCCP-induced [Mg2+]i increase in PC12 cells is mitochondria, and that mitochondrial depolarization triggers the Mg2+ release.

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“…In the study showing inhibition of lyase activity in hOGG1, Mg 2ϩ concentrations of 5 mmol/l were required for this effect. However, it has recently been shown that the concentration of Mg 2ϩ in mitochondria is ϳ1.2 mmol/l, and much of this Mg 2ϩ is bound to ATP (44). Therefore, it is unlikely that Mg 2ϩ concentrations in mitochondria will adversely affect hOGG1 lyase activity.…”

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“…Thus in cells, where the average potassium 118 Chapter 7. Conclusion ion concentration is about 140 mM [192] and the average magnesium concentration ranges from 0.05 to 1 mM [193,194], we can expect the head and tail domains to have a radius of 3 nm or larger. Furthermore, the concentration of ions in cells can have locally higher values thus leading to more accumulation in the head and tail domains and a greater effect on keratin filaments, bundles and networks.…”

“…They also correspond to the intracellular concentrations of 140 mM for potassium ions [192]. And in the case of magnesium ions, the intracellular concentration depends on the cell type and ranges from 0.05 to 1 mM [193,194].…”

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