Brooks 2018, The Science and Translation of Lactate Shuttle Theory

George Brooks’s review in Cell Metabolism (27(4):757–785) consolidates three decades of work into the lactate shuttle hypothesis: lactate is formed continuously under fully aerobic conditions, not only when oxygen is short, and is shuttled between and within cells to serve as fuel, as the major precursor for making glucose (the Cori cycle), and as a signalling molecule influencing gene expression and metabolism. A cell-to-cell shuttle carries lactate from producer cells such as fast-twitch fibres, through the blood, to consumer cells (slow-twitch fibres, heart, liver), while an intracellular shuttle moves it to the mitochondria; transport runs on monocarboxylate transporter (MCT) proteins whose density rises with endurance training, improving clearance. The definitive statement of the case that blood lactate is a marker of metabolic strain and a metabolic link, not an oxygen-starved waste product.