RT Journal Article
T1 Lactate sensing mechanisms in arterial chemoreceptor cells
A1 Torres-Torrelo, Hortensia
A1 Ortega-Sáenz, Patricia
A1 Gao, Lin
A1 López-Barneo, José
K1 Carotid body
K1 Reactive oxygen species
K1 Hypoxia
K1 Mitochondria
K1 Homeostasis
K1 Lactate dehydrogenase
K1 Chemoreceptor cells
K1 Cation Channels
K1 Cuerpo carotídeo
K1 Especies reactivas de oxígeno
K1 Hipoxia
K1 Mitocondrias
K1 Células quimiorreceptoras
AB Classically considered a by-product of anaerobic metabolism, lactate is now viewed as a fundamental fuel for oxidative phosphorylation in mitochondria, and preferred over glucose by many tissues. Lactate is also a signaling molecule of increasing medical relevance. Lactate levels in the blood can increase in both normal and pathophysiological conditions (e.g., hypoxia, physical exercise, or sepsis), however the manner by which these changes are sensed and induce adaptive responses is unknown. Here we show that the carotid body (CB) is essential for lactate homeostasis and that CB glomus cells, the main oxygen sensing arterial chemoreceptors, are also lactate sensors. Lactate is transported into glomus cells, leading to a rapid increase in the cytosolic NADH/NAD+ ratio. This in turn activates membrane cation channels, leading to cell depolarization, action potential firing, and Ca2+ influx. Lactate also decreases intracellular pH and increases mitochondrial reactive oxygen species production, which further activates glomus cells. Lactate and hypoxia, although sensed by separate mechanisms, share the same final signaling pathway and jointly activate glomus cells to potentiate compensatory cardiorespiratory reflexes.
PB Nature Publishing Group
YR 2021
FD 2021-07-06
LK http://hdl.handle.net/10668/4418
UL http://hdl.handle.net/10668/4418
LA en
NO Torres-Torrelo H, Ortega-Sáenz P, Gao L, López-Barneo J. Lactate sensing mechanisms in arterial chemoreceptor cells. Nat Commun. 2021 Jul 6;12(1):4166
DS RISalud
RD Apr 7, 2025