Torres-Torrelo, HortensiaOrtega-Sáenz, PatriciaGao, LinLópez-Barneo, José2022-11-282022-11-282021-07-06Torres-Torrelo H, Ortega-Sáenz P, Gao L, López-Barneo J. Lactate sensing mechanisms in arterial chemoreceptor cells. Nat Commun. 2021 Jul 6;12(1):4166http://hdl.handle.net/10668/4418Classically 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.enAtribución 4.0 InternacionalAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Carotid bodyReactive oxygen speciesHypoxiaMitochondriaHomeostasisLactate dehydrogenaseChemoreceptor cellsCation ChannelsCuerpo carotídeoEspecies reactivas de oxígenoHipoxiaMitocondriasCélulas quimiorreceptorasMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Anatomy::Cardiovascular System::Blood Vessels::ArteriesMedical Subject Headings::Anatomy::Nervous System::Neurons::Neurons, Afferent::Sensory Receptor Cells::Chemoreceptor Cells::Paraganglia, Nonchromaffin::Carotid BodyMedical Subject Headings::Anatomy::Cells::Neurons::Neurons, Afferent::Sensory Receptor Cells::Chemoreceptor CellsMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::HomeostasisMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Hydrogen-Ion ConcentrationMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Membrane Transport Proteins::Ion ChannelsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Hydroxy Acids::Lactates::Lactic AcidMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::MitochondriaMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::PhosphorylationMedical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Oxygen Compounds::Reactive Oxygen SpeciesMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical ProcessesMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Membrane Potentials::Action PotentialsMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::AnaerobiosisMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Phosphorylation::Oxidative PhosphorylationMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity::ExerciseMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Hydroxy Acids::LactatesMedical Subject Headings::Diseases::Bacterial Infections and Mycoses::Infection::Sepsisresearch article34230483open access10.1038/s41467-021-24444-72041-1723PMC8260783