Sodium Ion Regulates Mitochondrial ROS

In addition to the diverse well-known physiological functions and pathophysiological effects of sodium ion (Na⁺), regulation of mitochondrial reactive oxygen species (ROS) by Na⁺ has recently been demonstrated by several studies published in highly influential journals. The findings from these studies, especially the proposed “cytosolic Na⁺‒Na⁺/Ca²⁺ exchanger‒mitochondrial ROS” axis, have greatly broadened our understanding of this most popular element in physiology and disease. REFERENCES Kohlhaas M, Liu T, Knopp A, Zeller T, Ong MF, Bohm M, et al. Elevated cytosolic Na+ increases mitochondrial formation of reactive oxygen species in failing cardiac myocytes. Circulation 2010; 121(14):1606-13. doi: https://dx.doi.org/10.1161/CIRCULATIONAHA.109.914911. Dey S, DeMazumder D, Sidor A, Foster DB, O'Rourke B. Mitochondrial ROS drive sudden cardiac death and chronic proteome remodeling in heart failure. Circ Res 2018; 123(3):356-71. doi: https://dx.doi.org/10.1161/CIRCRESAHA.118.312708. Murphy E, Eisner DA. Regulation of intracellular and mitochondrial sodium in health and disease. Circ Res 2009; 104(3):292-303. doi: https://dx.doi.org/10.1161/CIRCRESAHA.108.189050. Adrogue HJ, Madias NE. Sodium and potassium in the pathogenesis of hypertension. N Engl J Med 2007; 356(19):1966-78. doi: https://dx.doi.org/10.1056/NEJMra064486. Hernansanz-Agustin P, Choya-Foces C, Carregal-Romero S, Ramos E, Oliva T, Villa-Pina T, et al. Na+ controls hypoxic signalling by the mitochondrial respiratory chain. Nature 2020; 586(7828):287-91. doi: https://dx.doi.org/10.1038/s41586-020-2551-y. Wolf SG, Mutsafi Y, Dadosh T, Ilani T, Lansky Z, Horowitz B, et al. 3D visualization of mitochondrial solid-phase calcium stores in whole cells. Elife 2017; 6. doi: https://dx.doi.org/10.7554/eLife.29929. Shadel GS, Horvath TL. Mitochondrial ROS signaling in organismal homeostasis. Cell 2015; 163(3):560-9. doi: https://dx.doi.org/10.1016/j.cell.2015.10.001. Oberkampf M, Guillerey C, Mouries J, Rosenbaum P, Fayolle C, Bobard A, et al. Mitochondrial reactive oxygen species regulate the induction of CD8+ T cells by plasmacytoid dendritic cells. Nat Commun 2018; 9(1):2241. doi: https://dx.doi.org/10.1038/s41467-018-04686-8. Sena LA, Li S, Jairaman A, Prakriya M, Ezponda T, Hildeman DA, et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity 2013; 38(2):225-36. doi: https://dx.doi.org/10.1016/j.immuni.2012.10.020.