(F) The boxed scheme describes the mitochondrial calcium overload hypothesis. Lactic acidosis forces the Na+/H+ exchanger (NHX) to import Na+, resulting in cytosolic Na+ overload. Subsequently, the Na+/Ca2+ exchanger (NCX) is forced into reverse mode to dispose of excess Na+, resulting in cytosolic calcium overload. This Ca2+ is then taken up by mitochondria, resulting in mitochondrial calcium overload. 2-DG (2-deoxyglucose; 50 mmol/L) blocks glycolysis through competitive hexokinase inhibition, whereas oligomycin (10 µmol/L) inhibits mitochondrial ATP synthase. G-6-P: glucose-6-phosphate. 