Cited by 127Mitochondrial Function and PathologyMetabolism, Diabetes, and CancerIon Transport and Channel Regulation

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Non-Canonical Control of Neuronal Energy Status by the Na+ Pump

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Baeza-Lehnert, Felipe, Saab, Aiman S., Gutiérrez, Robin, Larenas, Valeria, Díaz, Esteban, Horn, Melanie, Vargas, Miriam, Hösli, Ladina, Stobart, Jillian, Hirrlinger, Johannes, Weber, Bruno, Barros, L. Felipe·2019·Cell Metabolism

DOI 10.1016/j.cmet.2018.11.005

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Abstract

Neurons have limited intracellular energy stores but experience acute and unpredictable increases in energy demand. To better understand how these cells repeatedly transit from a resting to active state without undergoing metabolic stress, we monitored their early metabolic response to neurotransmission using ion-sensitive probes and FRET sensors in vitro and in vivo. A short theta burst triggered immediate Na+ entry, followed by a delayed stimulation of the Na+/K+ ATPase pump. Unexpectedly, cytosolic ATP and ADP levels were unperturbed across a wide range of physiological workloads, revealing strict flux coupling between the Na+ pump and mitochondria. Metabolic flux measurements revealed a "priming" phase of mitochondrial energization by pyruvate, whereas glucose consumption coincided with delayed Na+ pump stimulation. Experiments revealed that the Na+ pump plays a permissive role for mitochondrial ATP production and glycolysis. We conclude that neuronal energy homeostasis is not mediated by adenine nucleotides or by Ca 2+, but by a mechanism commanded by the Na+ pump.

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Authors: Baeza-Lehnert, F., Saab, A. S., Gutiérrez, R., Larenas, V., Díaz, E., Horn, M., Vargas, M., Hösli, L., Stobart, J., Hirrlinger, J., Weber, B., & Barros, L. F.
Affiliations: University of Zurich (CH)
Austral University of Chile (CL)
Centro de Estudios Científicos (CL)
Max Planck Institute of Experimental Medicine (DE)
Corresponding author: Barros, L. Felipe
ORCID: Saab, Aiman S.
Vargas, Miriam
Hösli, Ladina
Stobart, Jillian
Hirrlinger, Johannes
Weber, Bruno
Barros, L. Felipe
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2019-03
Volume: 29
Issue: 3
Pages: 668-680.e4
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2018.11.005
OpenAlex: W2904685632
Cited by: 126
References: 78
Citations by year: 2026: 10 · 2025: 19 · 2024: 25 · 2023: 21 · 2022: 12 · 2021: 12 · 2020: 13 · 2019: 14
FWCI: 3.47
Type: journal article
Language: en
Open access: bronze
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www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 370 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
Funders: FONDECYT (1160317)
University of Zurich
National Science Foundation
Centro de Estudios Científicos
Chilean Government
CONICYT
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords: Na+/K+-ATPase, mitochondrial energization, pyruvate, glycolysis, glucose utilization, ATP production, neurotransmission, theta burst stimulation, FRET biosensor, ion sensitive probe
MeSH terms: Sodium-Potassium-Exchanging ATPase, Adenosine Triphosphate, Animals, Astrocytes, Energy Metabolism, Glucose, Glycolysis, Homeostasis, Mice, Inbred C57BL, Mitochondria, Neurons

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Non-Canonical Control of Neuronal Energy Status by the Na+ Pump

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