Figure 1

Schematic view of the intracellular lactate shuttle with the mitochondrial lactate oxidation complex and the cell-to-cell lactate shuttle (CCLS). Myocytes have a glycolytic and an oxidative compartment. The glycolytic compartment in the cytosol is close to the myofibrils and their glycogen stores. It is associated with glycogenolysis/glycolysis and lactate release into the circulation. The oxidative compartment in close proximity to the mitochondria is considered responsible for lactate oxidation. Lactate produced in the cytosol is oxidized to pyruvate via the lactate oxidation complex in the mitochondria of the same cell. Pyruvate is then transported across the inner mitochondrial membrane via a monocarboxylate transport protein (MCT1). MCT1 is found in the mitochondrial inner membrane as part of the lactate oxidation complex together with its chaperone protein CD147, cytochrome oxidase (COX) and mitochondrial lactate dehydrogenase (mLDH). mLDH is found in the outer side of the inner membrane. Once pyruvate enters the mitochondrial matrix, it is metabolized by the tricarboxylic acid cycle (TCA). The CCLS hypothesis supports the idea that lactate produced in muscle can also serve as a substrate in highly oxidative cells (heart, brain) or contribute to gluconeogenesis (liver, kidney). cLDH, cytosolic lactate dehydrogenase.