Hypocalcemia and hypomagnesemia frequently occur under pathological conditions such as Crohn's disease or during diuretic treatment. However, how the combined deficiency of Ca2+ and Mg2+ affects cellular physiology has remained unclear. In this study, we focused on this issue and found that Ca2+/Mg2+ deprivation is a potent driver of stress granule (SG) formation. When SG formation was inhibited by G3BP1/2 knockdown, Ca2+/Mg2+ deprivation caused a further decrease in intracellular Mg2+ levels and an increase in cell death, indicating that SGs function to mitigate Mg2+ loss and protect cells from death under cation-deficient conditions. Furthermore, we found that the expression of the Mg2+ transporter MAGT1 is upregulated in an SG-dependent manner, and that MAGT1 knockdown further decreases intracellular Mg2+ levels and increases cell death. Collectively, our results demonstrate that SG formation acts as an adaptive mechanism to maintain Mg2+ homeostasis during Ca2+/Mg2+ deficiency.Key words: stress granule, MAGT1, magnesium, calcium.
Sakihara et al. (Thu,) studied this question.