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 be used as fuel, as the major precursor for making glucose, and as a signalling molecule. It is the definitive statement of the case that lactate is a metabolic link, not a waste product.
Key takeaways
- Lactate is produced continuously, at rest and during exercise, under fully aerobic conditions. Its appearance does not require a lack of oxygen.
- The cell-to-cell shuttle moves lactate from producer cells (such as fast-twitch fibres) through the blood to consumer cells (slow-twitch fibres, heart, liver) that oxidise it for energy or rebuild it into glucose.
- The intracellular shuttle moves lactate from the cytosol to the mitochondria within a single cell, where it is oxidised.
- Transport is carried out by monocarboxylate transporter (MCT) proteins; endurance training increases their density, improving clearance.
- Lactate is also a major gluconeogenic precursor (the Cori cycle) and a signalling molecule that influences gene expression and metabolism.
- Blood lactate is better read as a marker of metabolic strain than of oxygen-starved stress, which reframes how it is interpreted in both sport and clinical settings.