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Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism
Open accessAbstract
The brain’s energy demands are remarkable both in their intensity and in their moment-to-moment dynamic range. This perspective considers the evidence for Warburg-like aerobic glycolysis during the transient metabolic response of the brain to acute activation, and it particularly addresses the cellular mechanisms that underlie this metabolic response. The temporary uncoupling between glycolysis and oxidative phosphorylation led to the proposal of an astrocyte-to-neuron lactate shuttle whereby during stimulation, lactate produced by increased glycolysis in astrocytes is taken up by neurons as their primary energy source. However, direct evidence for this idea is lacking, and evidence rather supports that neurons have the capacity to increase their own glycolysis in response to stimulation; furthermore, neurons may export rather than import lactate in response to stimulation. The possible cellular mechanisms for invoking metabolic resupply of energy in neurons are also discussed, in particular the roles of feedback signaling via adenosine diphosphate and feedforward signaling by calcium ions.
Overview
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Written from the paper’s full text.
TL;DR
Yellen reviews how neuronal metabolism acutely balances glycolysis and oxidative phosphorylation during stimulation, arguing that activated neurons increase glucose rather than lactate utilization and that the classical astrocyte-to-neuron lactate shuttle does not provide the primary neuronal energy source during activation. It also outlines unresolved mechanisms controlling glycolysis/oxphos coupling, including ADP/Ca²⁺ signaling and cytosolic NADH redox.
Key findings
- In resting brain, glycolysis and oxphos are near matched: the oxygen–glucose index is ∼5.5 in gray matter versus an ideal stoichiometry of 6, and the brain is ∼2% of body mass but consumes ∼20% of the daily energy budget; neurons account for most (∼80–90%) of the brain’s energy demand.
- During stimulation, there is transient uncoupling: local blood flow increases by ∼50% with commensurate local glucose consumption, but oxygen utilization increases much less, on the order of 5%, reducing OGI to ∼5; lactate rises locally and can be exported with strong stimuli such as seizures.
- Evidence favors direct neuronal glycolysis during activation rather than lactate uptake: stimulation increased glucose metabolism over twofold while lactate metabolism declined in cultured neurons, and neuronal cytosolic NADH/NAD⁺ transients in hippocampal/cortical neurons rise for ∼2–3 min and are blocked by glycolysis inhibition but not by MCT or LDH blockade, suggesting neurons normally export lactate when stimulated.
- The ANLS hypothesis remains controversial: astrocytes are more glycolytic at rest with higher cytosolic NADH/NAD⁺, and lactate shuttling may support resting or ischemic conditions, but the paper states there is no affirmative evidence that astrocyte-to-neuron lactate movement occurs during ordinary brain activation.
Methods
- Review/perspective article, not primary research; it synthesizes biochemical, imaging, genetic, and metabolic literature.
- Discusses studies using cultured neurons and astrocytes, acute brain slices, in vivo rodent cortex/hippocampus, retina, white matter, Drosophila, and human PET/MRS/functional imaging.
- Main analysis is a narrative synthesis organized around two questions: the balance between glycolysis and oxphos in brain cells, and the cellular mechanisms responsible for acute control of glycolysis and oxphos in neurons.
Limitations
- The paper states many caveats for OGI measurements: pentose phosphate pathway and glycogen synthesis can consume glucose without oxygen; stress, stimulus strength, region definition, lactate oxidation in surrounding tissue, and β-adrenergic blockade can affect results; ANLS evidence often argues feasibility rather than direct occurrence.
- The paper states that understanding of oxphos-related mitochondrial signals and the trigger for neuronal glycolysis is incomplete; mechanisms may vary with stimulation degree, glucose/O₂ conditions, and cell type, and more compartment- and cell-specific studies are needed.
- Evident from the text: as a review, it presents no systematic search or meta-analysis and no new primary data; conclusions depend on cited studies with differing preparations and limitations, including glucose analogues with different transport properties, MCT blockers that also affect mitochondrial pyruvate uptake, and culture conditions that may alter metabolic behavior.
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Claims the paper makes
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In the paper
“the focus will be on neurons which comprise most (∼80–90%) of the energy demand of the brain (Attwell and Laughlin, 2001; Yu et al., 2017).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > Definitions > Oxidative phosphorylation (oxphos)
What the sources say
- Not checked yetcites Attwell and Laughlin, 2001 source
- Not checked yetcites Yu et al., 2017
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In the paper
“For instance, if the unstimulated tissue in the periphery or even within the stimulated region is capable of oxidative metabolism of the excess lactate (Madsen et al., 1999; Gandhi et al., 2009), then including the contribution from this tissue will normalize the OGI.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Transient uncoupling between glycolysis and oxphos during brain activation
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Second, OGI may be exaggerated or suppressed depending on how the stimulated region is defined.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Transient uncoupling between glycolysis and oxphos during brain activation
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“This is supported by measurements showing local elevation of brain lactate levels with stimulation (Korf and de Boer, 1990; Hu and Wilson, 1997; Mazuel et al., 2017) and even lactate export from the brain (e.g., Duffy et al., 1975, with stronger stimuli such as epileptic seizures).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Transient uncoupling between glycolysis and oxphos during brain activation
What the sources say
- Not checked yetcites Duffy et al., 1975 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Experiments in support of the ANLS often argue for its feasibility rather than providing direct evidence that it occurs.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“This is supported by measurements showing local elevation of brain lactate levels with stimulation (Korf and de Boer, 1990; Hu and Wilson, 1997; Mazuel et al., 2017) and even lactate export from the brain (e.g., Duffy et al., 1975, with stronger stimuli such as epileptic seizures).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Transient uncoupling between glycolysis and oxphos during brain activation
What the sources say
- Not checked yetcites Korf and de Boer, 1990
- Not checked yetcites Hu and Wilson, 1997
- Not checked yetcites Mazuel et al., 2017 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Finally, consistent with stress contributing to the reduced OGI, β-adrenergic blockade by propranolol reduces or eliminates the stimulation-induced change in OGI (Dienel and Cruz, 2016).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Transient uncoupling between glycolysis and oxphos during brain activation
What the sources say
- Not checked yetcites Dienel and Cruz, 2016
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“In contrast, the brain’s tricarboxylic acid (TCA) cycle is fed mainly by metabolites derived from circulating glucose, with relatively little intermediate mixing of lactate from the circulation.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Near-stoichiometric utilization of oxygen and glucose in resting brain
What the sources say
- Not checked yetcites Hui et al., 2017 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“The best estimates for the oxygen–glucose index (OGI; OGI = CMRO2/CMRglc) in the resting brain is around ∼5.5 in gray matter (Clarke and Sokoloff, 1994; Hyder et al., 2013), very close to the ideal stoichiometry of 6.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Near-stoichiometric utilization of oxygen and glucose in resting brain
What the sources say
- Not checked yetcites Clarke and Sokoloff, 1994
- Not checked yetcites Hyder et al., 2013 source
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“The overall OGI is reduced from the near-stoichiometric values down to ∼5 (Madsen et al., 1999).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Transient uncoupling between glycolysis and oxphos during brain activation
What the sources say
- Not checked yetcites Madsen et al., 1999 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 18
- It may state two separate claims as one. 38
None of the sources cited for this claim have been checked yet.
In the paper
“The ANLS hypothesis has been quite controversial for a long time (Chih et al., 2001; Gjedde and Marrett, 2001; Hertz, 2004; Mangia et al., 2011; Dienel, 2012, 2017; Bak and Walls, 2018; Barros and Weber, 2018; see also Dienel [2017] for strong arguments against ANLS at the tissue level).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Recent work on in vivo metabolite fluxes argues that uncoupling between glycolysis and oxidative metabolism is the norm for all organs except the brain (Hui et al., 2017).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Near-stoichiometric utilization of oxygen and glucose in resting brain
What the sources say
- Not checked yetcites Hui et al., 2017 source
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“But the increase in oxygen utilization is much less, on the order of 5%, indicating that the additional glucose consumption is not stoichiometrically matched by oxygen but rather that glucose is metabolized nonoxidatively by glycolysis without oxphos.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Transient uncoupling between glycolysis and oxphos during brain activation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Nevertheless, multiple studies exhibit net production of lactate from glucose in activated brain, arguing that glycolysis without oxphos constitutes a component of the reduced OGI (Korf and de Boer, 1990; Hu and Wilson, 1997; Mazuel et al., 2017).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Transient uncoupling between glycolysis and oxphos during brain activation
What the sources say
- Not checked yetcites Korf and de Boer, 1990
- Not checked yetcites Hu and Wilson, 1997
- Not checked yetcites Mazuel et al., 2017 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Other organs readily export the lactate they derive from glucose metabolism, and they readily use circulating lactate for their oxidative metabolism.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Near-stoichiometric utilization of oxygen and glucose in resting brain
What the sources say
- Not checked yetcites Hui et al., 2017 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“With regional stimulation (e.g., of the visual cortex by a flashing checkerboard pattern), positron electron tomography studies reveal that local blood flow increases by ∼50% and that there is a commensurate increase in local glucose consumption.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Transient uncoupling between glycolysis and oxphos during brain activation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The expected stoichiometry for this process is that six O2 molecules will be consumed for each glucose molecule.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Near-stoichiometric utilization of oxygen and glucose in resting brain
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“First, in addition to glycolysis, the pentose phosphate pathway and glycogen synthesis can both result in net utilization of glucose without molecular oxygen, thereby reducing the OGI.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > Transient uncoupling between glycolysis and oxphos during brain activation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“For instance, the initial demonstration of feasibility was from separately cultured astrocytes and neurons: glutamate application to cultured astrocytes triggers [3H]-2-deoxyglucose (2-DG; [3H]–2-DG) uptake and lactate release, and neurons are capable of consuming lactate as a fuel (Magistretti et al., 1993; Pellerin and Magistretti, 1994).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
- Not checked yetcites Magistretti et al., 1993 source
- Not checked yetcites Pellerin and Magistretti, 1994
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Two recent in vivo studies monitored glucose analogue accumulation in somatosensory cortex during whisker stimulation; they used two different glucose analogues and obtained opposite results.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- The authors state this as an assumption: Uptake of 2-DG-based tracers and, in some cases, their phosphorylation by hexokinase parallels glucose utilization.
None of the sources cited for this claim have been checked yet.
In the paper
“Glycolysis is one of the most ancient metabolic pathways with a wide variety of allosteric and phosphorylation-based controls (Mulukutla et al., 2010; Icard and Lincet, 2012).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
- Not checked yetcites Mulukutla et al., 2010 source
- Not checked yetcites Icard and Lincet, 2012
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Importantly, this study was done with unstimulated neurons and did not test whether the preferential use of lactate was enhanced by activation as proposed (Bouzier-Sore et al., 2006).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
- Not checked yetcites Bouzier-Sore et al., 2006 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In vitro glycolytic behavior can change with choice of culture media (Sünwoldt et al., 2017) and astrocyte coculture (Mamczur et al., 2015), but gene expression data from acutely dissociated brain cells indicate that neurons are well equipped for glycolysis, with higher levels of mRNA expression than astrocytes for most glycolytic enzymes (Fig. 1, left).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
Strength:plain· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“although again, the transporters are both equilibrative, and transcriptomics show comparable levels of MCT1 in both neurons and astrocytes (Fig. 1, left; the proteomics data on the right show an overall deficit of MCTs in neurons, but they are from cells in culture).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
- Not checked yetcites Fig. 1
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Similar experiments using graded neuronal stimulation by NMDA, which produced moderate submicromolar increases in cytosolic calcium, showed that activation increased glucose metabolism over twofold, whereas lactate metabolism declined, consistent with a role for extracellular lactate supporting basal metabolism in neurons but not stimulated activity (Bak et al., 2009).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
- Not checked yetcites Bak et al., 2009 source
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Similar experiments using graded neuronal stimulation by NMDA, which produced moderate submicromolar increases in cytosolic calcium, showed that activation increased glucose metabolism over twofold, whereas lactate metabolism declined, consistent with a role for extracellular lactate supporting basal metabolism in neurons but not stimulated activity (Bak et al., 2009).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
- Not checked yetcites Bak et al., 2009 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Although one specific enzyme for up-regulation of glycolysis, the bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (isoform PFKFB3), is posttranslationally down-regulated in neurons and thus cannot participate in glycolytic stimulation (Herrero-Mendez et al., 2009; Bolaños, 2016), this rules out only one of many mechanisms that neurons can use to stimulate glycolysis.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“The NADHCYT transients decrease with inhibition of glycolysis but not of the MAS, indicating that increased neuronal glycolysis upon stimulation is the main cause of the NADHCYT transients.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
- Not checked yetcites Díaz-García et al., 2017 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, neighboring cells are capable of maintaining very different NADHCYT redox, and at rest, the high NADHCYT of astrocytes does not drive neighboring neurons to a correspondingly high level.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear? Based: unclearIt may state two separate claims as one.
In the paper
“A deliberate review of the evidence with an optimized model concluded that neurons provide about a third of their own lactate/pyruvate during brain activation, with the other two thirds from astrocytes (Hyder et al., 2006).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
- Not checked yetcites Hyder et al., 2006 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- The authors state this as an assumption: Acetate is metabolized only in glia.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In essence, the very active malate–aspartate shuttle (MAS) of neurons could transfer reducing equivalents not only from neuronal glycolysis but also from astrocytic glycolysis.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“In Drosophila melanogaster, glycolysis appears to be more essential in glial cells than it is in neurons; knockdown of glycolytic enzymes in neurons did not affect the viability or the general behavior of flies, whereas knockdown in glial cells produced noticeable phenotypic changes (Volkenhoff et al., 2015).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
- Not checked yetcites Volkenhoff et al., 2015 source
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the opposite appears to be true: photoreceptors perform aerobic glycolysis and export lactate, which is then oxidized by Müller cells (Hurley et al., 2015; Kanow et al., 2017).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Baseline accumulation of the analogue into astrocytes and neurons was similar; upon whisker stimulation in anesthetized rats, uptake into both cell types tended to increase, though only significantly for astrocytes (Chuquet et al., 2010).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
- Not checked yetcites Chuquet et al., 2010 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- The authors state this as an assumption: Uptake of 2-DG-based tracers and, in some cases, their phosphorylation by hexokinase parallels glucose utilization.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The acute metabolic response to neuronal activity has not been studied.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At present, there are no data to indicate whether there is significant redox exchange between astrocytes and neurons through lactate–pyruvate exchange.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Moderate chemical stimulation produced a strong increase in the labeling of glutamate from labeled glucose and a decrease in the incorporation of label from labeled lactate, inconsistent with significant lactate utilization by neurons during stimulation.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Consistent with most of the cultured cell studies, in resting brain or in quiescent brain slice astrocytes appear to be more glycolytic than neurons, with higher resting cytosolic NADH/NAD+ (NADHCYT) ratios (Mongeon et al., 2016) that predispose them to higher resting lactate/pyruvate ratios and higher resting lactate levels (Mächler et al., 2016).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
- Not checked yetcites Mächler et al., 2016 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Müller cells are deficient in pyruvate kinase, the final enzyme in the glycolytic pathway, and have limited ability to convert glucose to lactate (Lindsay et al., 2014).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
- Not checked yetcites Lindsay et al., 2014 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Furthermore, although in cultured neurons, unlabeled lactate does not diminish the increased utilization of labeled glucose with stimulation, it does reduce labeling from glucose at rest (Bak et al., 2009).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
- Not checked yetcites Bak et al., 2009 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In neuronal cell bodies, stimulation leads to enhanced neuronal glucose metabolism,”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
In the paper
“But the absence of mitochondria from dendritic spines does make it questionable whether the role of MCTs, which may be inserted into spine membranes together with AMPA receptors (Bergersen et al., 2001), is to support astrocyte-to-neuron movement of lactate rather than efflux of lactate produced by aerobic glycolysis in the spines.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
What the sources say
- Not checked yetcites Bergersen et al., 2001 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both the increased O2 consumption and the initial NAD(P)H dip are generally agreed to reflect increased ETC activity upon mitochondrial depolarization,”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos? > ADP and Ca2+ can both depolarize mitochondria
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A complication in dissecting the roles of these two avenues for metabolic regulation is that Ca2+ handling is itself metabolically expensive, so elevated [Ca2+] is usually accompanied by an elevation in ADP.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos?
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Clearly, we do not have a complete understanding of the oxphos-related mitochondrial signals that result from neuronal excitation.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos? > ADP and Ca2+ can both depolarize mitochondria
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“whereas in some myelinated axons, metabolic support from glia may be essential during stimulation.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both of these agents can regulate glycolysis and oxphos rates via multiple mechanisms.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos?
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
In the paper
“This feedforward effect of Ca2+ would increase the rate of matrix NADH production (and thus the NAD(P)H signal) and thereby increase the supply of electrons for the ETC, leading to mitochondrial hyperpolarization (Ivannikov and Macleod, 2013).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos? > ADP and Ca2+ can both depolarize mitochondria
What the sources say
- Not checked yetcites Ivannikov and Macleod, 2013
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The depolarization and proton movements accompanying ADP or Ca2+ entry will diminish ΔμH and allow the stalled ETC to function again, consuming O2 and matrix NADH (Fig. 2).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos? > ADP and Ca2+ can both depolarize mitochondria
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, there is no affirmative evidence that lactate movement from astrocytes to neurons occurs during the ordinary function of the brain, particularly during brain stimulation.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What is the balance in brain between glycolysis and oxphos? > The source of neuronal energy during activation
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
In the paper
“However, it is hard to reconcile this with the clear finding by Shuttleworth et al. (2003) that the NAD(P)H overshoot in slices did not disappear with the prolonged elimination of extracellular Ca2+, although the mitochondrial Ca2+ transient did disappear.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos? > ADP and Ca2+ can both depolarize mitochondria
What the sources say
- Not checked yetcites Shuttleworth et al., 2003 source
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ADP can be considered a feedback metabolic signal—energetic costs have been incurred and must be paid for—whereas Ca2+ can function as a feedforward signal to anticipate energetic costs before they are incurred.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos?
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Also, for glycolysis and oxphos to run at different rates, there must be slippage or uncoupling at the interface between them: lactate-pyruvate partitioning controlled by the NADHCYT ratio.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos?
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Proximally, both produce depolarization (diminution) of the mitochondrial membrane potential (Δψ) and the related mitochondrial proton driving force (ΔμH; Fig. 2 A).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos? > ADP and Ca2+ can both depolarize mitochondria
What the sources say
- Not checked yetcites Nicholls and Ferguson, 2002
- Not checked yetcites Salway, 2004
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The shuttle is the primary route for moving reducing equivalents across the mitochondrial inner membrane (because NADH itself does not cross).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos? > Partitioning between lactate production and pyruvate oxidation depends on NADHCYT
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both of these effects suggest that elevated NADHCYT by itself can both affect glucose flux through glycolysis and shunt pyruvate toward lactate and away from utilization for oxphos.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos? > Partitioning between lactate production and pyruvate oxidation depends on NADHCYT
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Neurons possess many mitochondria and rely chronically on them as a major source of ATP (Hall et al., 2012),”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > Some key puzzles to solve
What the sources say
- Not checked yetcites Hall et al., 2012 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the most direct evidence argues that upon neuronal stimulation, the classical ANLS hypothesis does not apply and that instead, there is an increase in neuronal glycolysis accompanied by a smaller increase in neuronal oxphos.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > Some key puzzles to solve
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“First, glycolysis produces NADH at the GAPDH step. This NADH will accumulate in the cell (and ultimately inhibit continued glycolysis) unless it is recycled by one of two recycling routes. The first is LDH: conversion of NADH to NAD+ coordinately with production of lactate from pyruvate; this is the primary mechanism by which cells can perform glycolysis without oxphos, as it deprives mitochondria”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos? > Partitioning between lactate production and pyruvate oxidation depends on NADHCYT
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“In dentate granule neurons, MCT inhibition led to higher peaks of NADHCYT as well as smaller dips in glucose, suggesting that the elevated NADHCYT also exerted back pressure on glycolysis, presumably on the GAPDH equilibrium (Díaz-García et al., 2017).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos? > Partitioning between lactate production and pyruvate oxidation depends on NADHCYT
What the sources say
- Not checked yetcites Díaz-García et al., 2017 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mechanisms that are engaged by neuronal excitation can vary with the degree of stimulation and with the environmental conditions of [glucose] and [O2] during experiments, which usually vary from the in vivo condition, and the mechanisms may also vary with cell type.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos? > ADP and Ca2+ can both depolarize mitochondria
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because interconversion between pyruvate and lactate by LDH requires coordinate interconversion between NADH and NAD+, and because the rate of glycolysis depends on some form of recycling of NADH to NAD+, the NADHCYT ratio is a key parameter for the uncoupling.”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > What are the contributors to controlling the balance between glycolysis and oxphos? > Partitioning between lactate production and pyruvate oxidation depends on NADHCYT
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“fast-twitch muscle, requiring the greatest acute supply of energy, tends to be far more glycolytic and to have fewer mitochondria than the slow-twitch muscle used for postural control (Crow and Kushmerick, 1982; Spriet, 1989).”
§ Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism > Some key puzzles to solve
What the sources say
- Not checked yetcites Crow and Kushmerick, 1982
- Not checked yetcites Spriet, 1989
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The authors state this as an assumption.
Uptake of 2-DG-based tracers and, in some cases, their phosphorylation by hexokinase parallels glucose utilization.
“Glucose uptake by neurons and astrocytes can be monitored with tracers based on 2-DG, relying on the assumption that uptake of the tracers and (in some cases) their phosphorylation by hexokinase parallels glucose utilization.”
The authors state this as an assumption.
Acetate is metabolized only in glia.
“However, this conclusion depends on the assumption that acetate is metabolized only in glia; a recent study of acetate metabolism in brain slices showed a substantial ability of neurons to metabolize acetate directly, which calls the compartment-specific modeling into question (Rowlands et al., 2017).”
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Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“neuronal activity and glucose utilization have previously been shown to exist in a near 1:1 stoichiometric relationship72”
From APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice (2020) · cites this paper as [72]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“As the two most abundant, and energetically most essential cell types in the brain, neuron and astrocyte are coupled in not only glucose oxidation (Magistretti and Allaman, 2018; Yellen, 2018), but also lipid metabolism (Barber and Raben, 2019).”
From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Yellen, 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The capacity in performing glycolysis and OXPHOS varies between neuron and astrocyte (Magistretti and Allaman, 2018; Yellen, 2018).”
From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Yellen, 2018
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The high metabolic need of the brain cannot be met by glycolytic activity. Rather, neurons rely on the tricarboxylic acid cycle and oxidative phosphorylation housed in mitochondria to produce ATP [72,120].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [72]
Citations
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“Is it through feedback regulation of the glycolytic enzymes by changes in cytosolic ATP, ADP, and AMP or through feedforward regulation by intracellular Ca2+ (and if so, through which of many possible signaling pathways)?”
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BackgroundUnderstanding the Intersections between Metabolism and Cancer Biology
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Research works printed but not linked: 3
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- Nelson, 2017, Lehninger Principles of Biochemistry.
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Targeting mitochondrial Ca2+ uptake for the treatment of amyotrophic lateral sclerosis
Zhong, R., Rua, M. T., & Wei‐LaPierre, L. (2023) · The Journal of Physiology · doi:10.1113/jp284143 · Cited by 12
“However, what energy system the activity-driven ATP synthesis relies on has been the centre of debate (Yellen, 2018).”
BackgroundChen, C.-Y., Chou, F.-Y., Chang, Y., Ho, C., Wu, K.-C., Hsu, C., Chern, Y., & Lin, C. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106004 · Cited by 11
“Neuronal ATP production may depend on the glycolysis and oxidative phosphorylation (OXPHOS) pathways (Yellen, 2018).”
Icaritin greatly attenuates β‐amyloid‐induced toxicity in vivo
Li, L., Wei, Z., Tang, Y., Jin, M., Yao, H., Li, X., Li, Q., Tan, J., & Xiao, B. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14527 · Cited by 11
“53 ATP synthase, also known as “Complex V", is the terminal enzyme in the oxidative phosphorylation pathway.”
BackgroundPersistent changes in extracellular lactate dynamics following synaptic potentiation
Bingul, D., Kalra, K., Murata, E. M., Belser, A., & Dash, M. B. (2020) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2020.107314 · Cited by 13
“…in extracellular lactate concentration is typically observed (Hu and Wilson, 1997; Caesar et al., 2008; Li and Freeman, 2015), although the origin and functional consequences of these increases remain contested (Dienel, 2013, 2017; Bak and Walls, 2018; Magistretti and Allaman, 2018; Yellen, 2018).”
BackgroundInfluentialBertling, E., Blaesse, P., Seja, P., Kremneva, E., Gateva, G., Virtanen, M. A., Summanen, M., Spoljaric, I., Uvarov, P., Blaesse, M., et al. (2021) · EMBO Reports · doi:10.15252/embr.202050145 · Cited by 9
A Network Architecture for Bidirectional Neurovascular Coupling in Rat Whisker Barrel Cortex
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ABCA7 Loss-of-Function Variants Impact Phosphatidylcholine Metabolism in the Human BrainPreprint
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“These observations are consistent with previous observations in vivo (Mangia et al. 2009) and in hippocampal slices (Diaz-Garcia et al. 2017; Yellen 2018) and not only suggest that neurons can be net producers of lactate, but also that neurons can release lactate and hereby contribute to the surge…”
Bioenergetics of Axon Integrity and Its Regulation by Oligodendrocytes and Schwann Cells
Mishra, S. K., & Tiwari, S. P. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-03950-x · Cited by 10
“These reducing equivalents are processed by electron transport chain enzymes and energy in the form of ATP is generated through a process called as oxidative phosphorylation, which is utilized to perform various neuronal functions [16].”
Hammer, M. F., Krzyzaniak, C. T., Bahramnejad, E., Smelser, K., Hack, J., Watkins, J. C., & Ronaldson, P. T. (2024) · Clinical Science · doi:10.1042/cs20231572 · Cited by 10
“While rates of glycolysis and OXPHOS are well matched in the resting brain, neuronal stimulation can cause a Warburg-like transient dissociation between glycolysis and OXPHOS in response to increased energy demand [83].”
Sharma, A., Sah, N., Sharma, R. B., Vyas, P., Liyanage, W., Kannan, S., & Kannan, R. M. (2024) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10655 · Cited by 10
Pourmajidian, M., Hansen, J. Y., Shafiei, G., Mišić, B., & Dagher, A. (2026) · PLoS Biology · doi:10.1371/journal.pbio.3003619 · Cited by 11
Szabo, L., Grimm, A., García‐León, J. A., Verfaillie, C. M., & Eckert, A. (2023) · Cells · doi:10.3390/cells12101385 · Cited by 9
“Subsequently, pyruvate enters mitochondria Cells 2023, 12, 1385 17 of 25 and is converted into acetyl-CoA, which reaches the tricarboxylic acid (TCA) cycle within the mitochondrial matrix, ultimately resulting in the formation of additional NADH out of NAD+ and FADH2 from FAD [48].”
BackgroundGonzalez-Vazquez, A., Aguilar-Peralta, A. K., Tomás-Sanchez, C., Blanco-Álvarez, V. M., Martínez‐Fong, D., González-Barrios, J. A., Treviño, S., Peña, L. M.-P., Alatriste, V., Soto-Rodríguez, G., et al. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6696538 · Cited by 9
“AST and ALT play an essential role in maintaining the energy metabolism in most tissues, including neonatal and adult cerebral tissue [17, 18].”
BackgroundFeng, Y., Chen, X., Zhang, X. D., & Huang, C. (2023) · Genes · doi:10.3390/genes14061285 · Cited by 9
“Among these metabolism pathways, oxidative phosphorylation (Figure 2e) plays a crucial role in brain cell energy metabolism [56] and has been shown to be involved in the pathogenesis of AD [57].”
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“Functionally, biochemical investigations also offer molecular insights into individual mt pathways, including OXPHOS, protein folding assemblies in each mt subcompartment, translocation machineries in the outer (TOM) and inner (TIM) membranes, and complexes required for the regulation of the dynamic behavior of mt and…”
BackgroundInfluentialZeng, M., He, Y. T., Zhou, H., Du, H., Shao, C., Yang, J., & Wan, H. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118766 · Cited by 9
Metabolic Reprogramming in Nerve Cells
Bhattacharya, S. (2023) · American Journal of Biomedical Science & Research · doi:10.34297/ajbsr.2023.18.002444 · Cited by 8
Neurometabolic predictors of mental effort in the frontal cortex
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“Recent advances emphasize the importance of brain bioener-getic and metabolic processes for brain function, behavior, and cognition [16 – 18].”
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“Neuronal activation associates with a high energy demand and requires sufficient supply of glucose (D-glucose) and oxygen for the synthesis of adenosine- 5′-triphosphate (ATP) in glycolysis and oxidative metabolism in mitochondria (Dienel 2019a; Kann and Kovács 2007; Yellen 2018).”
Neuroprotective effects of violacein in a model of inherited amyotrophic lateral sclerosis
Olivera‐Bravo, S., Bolatto, C., Damianovich, G. O., Stancov, M., Cerri, S., Rodríguez, P., Boragno, D., Mir, K. H., Cuitiño, M. N., Larrambembere, F., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-06470-7 · Cited by 9
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Analysis of mitochondrial respiration and ATP synthase in frozen brain tissues
Yao, P. J., Munk, R. B., Gorospe, M., & Kapogiannis, D. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e13888 · Cited by 8
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“amino-acids) could be done(220) and that some typical routes, via remained adjacent oligodendrocytes and astrocytes, left unaffected by ODS in the same murine model, reached the resilient neuron cell bodies because, the dependence of traumatized neurons on glycolysis and oxidative phosphorylation remained unclear.(220…”
BackgroundNeuronal glycolysis: focus on developmental morphogenesis and localized subcellular functions
Gallo, G. (2024) · Communicative & Integrative Biology · doi:10.1080/19420889.2024.2343532 · Cited by 7
“The absence of astrocytes during the major period of neuronal development and establishment of cerebral vasculature obviates the likelihood of an astro-cyte-based lactate shuttle [6–9] being operative supporting the bioenergetic needs of developing neurons.”
BackgroundThe cation exchanger Letm1, circadian rhythms, and NAD(H) levels interconnect in diurnal zebrafish
Dao, P., Hajny, S., Mekis, R., Orel, L., Dinhopl, N., Tessmar‐Raible, K., & Nowikovsky, K. (2022) · Life Science Alliance · doi:10.26508/lsa.202101194 · Cited by 8
“In the brain of letm1(+/−) mice, an increase of glycolytic metabolites and a reduced activity of the Ca2+-sensitive pyruvate dehydrogenase (PDH), the first enzyme that commits cells to glucose oxidation was detected, as well as decreased metabolites of the de novo biosynthesis of NAD+, tryptophan, and quinolate and re…”
BackgroundInfluentialDienel, G. A., & Rothman, D. L. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15775 · Cited by 9
“Studies in cultured neurons and brain slices also support increased neuronal glucose uptake, glycolysis, and lactate production, not lactate uptake, under activating conditions (Ashrafi et al., 2017; Ashrafi & Ryan, 2017 ; Diaz-Garcia et al., 2017 ; Diaz-Garcia & Yellen, 2019; Yellen, 2018 ).”
BackgroundA suite of neurophotonic tools to underpin the contribution of internal brain states in fMRI
Mächler, P., Broggini, T., Matéo, C., Thunemann, M., Fomin-Thunemann, N., Doran, P. R., Şencan, İ., Kılıç, K., Desjardins, M., Uhlířová, H., et al. (2021) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2021.100273 · Cited by 6
Microscopic Quantification of Oxygen Consumption across Cortical LayersPreprint
Mächler, P., Fomin-Thunemann, N., Thunemann, M., Sætra, M. J., Desjardins, M., Kılıç, K., Şencan, İ., Li, B., Saisan, P. A., Cheng, Q., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.13.464176 · Cited by 6
“Beyond this reserve, upregulation in aerobic glycolysis may play a role alongside oxidative phosphorylation to rapidly supply ATP (Dienel 2019, Raichle & Mintun 2006, Yellen 2018).”
BackgroundMitochondrial Ca 2+ efflux controls neuronal metabolism and long-term memory across speciesPreprint
Vishwanath, A. A., Comyn, T., Chintaluri, C., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.01.578153 · Cited by 7
Glial metabolism versatility regulates mushroom body–driven behavioral output inDrosophilaPreprint
Basu, R., Préat, T., & Plaçais, P.-Y. (2024) · Learning & Memory · doi:10.1101/lm.053823.123 · Cited by 7
“Thus, despite still-ongoing debate and controversies (Dienel 2017; Bak and Walls 2018; Yellen2018), bolstered by parallel experimental evidence thatneu-ronal glycolysis can also support brain activity (Bak et al. 2009; Ashra fi et al. 2017; Díaz-García et al. 2017), it can be stated that a major,…”
BackgroundTheriault (n.d.) · doi:10.31234/osf.io/pkzr8 · Cited by 51
Synaptic-mitochondrial transport: mechanisms in neural adaptation and degeneration
Ding, Y., Yang, H., Gao, J., Tang, C. L., Peng, Y.-Y., Ma, X., Li, S., Wang, H., Lu, X., & Wang, Y. (2025) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-025-05209-y · Cited by 7
Glucose Metabolism, Lactate, Lactylation and Alzheimer’s Disease
Hai, S., Hou, Y., Zhang, M., Gao, X., Yang, T., Shang, X., & Sun, X. (2025) · Aging and Disease · doi:10.14336/ad.2025.0338 · Cited by 9
“Even in the presence of sufficient oxygen, cells such as astrocytes and highly active neurons can generate lactate through "aerobic glycolysis," often referred to as the Warburg effect [45].”
Alves, V. S., & Oliveira, F. A. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122554 · Cited by 6
Deciphering the brain glucose metabolism: A gateway to innovative stroke therapies
Pisani, D. F., & Blondeau, N. (2025) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x251346277 · Cited by 11
“26,27 We can suppose that the increased activity of LDH1 at the detriment of LDH5 potentially limits G3PDH activity due in part to a low NAD þ /NADH ratio, which could limit complete glucose oxidation by glycolysis in favour of the lactate/pyruvate way (Figure 1).”
Thomas, R., Hallett, P. J., & Ole Isacson, A. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.02.004 · Cited by 6
Gola, L., Bierhansl, L., Hummel, N., Korn, L., Pawlowski, M., Cerina, M., Hundehege, P., Budde, T., König, S., Meuth, S. G., et al. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.12.010 · Cited by 5
Shoemaker, R. C. (2020) · Trends in Diabetes and Metabolism · doi:10.15761/tdm.1000118 · Cited by 6
Monocarboxylate Transport in Drosophila Larval Brain during Low and High Neuronal ActivityPreprint
González‐Gutiérrez, A., Ibacache, A., Esparza, A., Barros, L. F., & Sierralta, J. A. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/610196 · Cited by 6
MLKL overexpression leads to Ca2+ and metabolic dyshomeostasis in a neuronal cell model
Deepa, S. S., Thadathil, N., Corral, J., Mohammed, S., Pham, S., Rose, H., Kinter, M. T., Richardson, A. G., & Díaz‐García, C. M. (2024) · Cell Calcium · doi:10.1016/j.ceca.2024.102854 · Cited by 6
Kanaan, M. N., Karam, C. Y., Kennedy, L. S., Pileggi, C. A., Hamilton, L., Čuperlović‐Culf, M., & Harper, M. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103839 · Cited by 6
“However, this is an energetically costly process with glycolysis serving as the primary energy source for this process [110,111].”
Zhang, R., Zhang, M., Xie, Y., et al. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104139 · Cited by 5
“J. Bar graphs of Nissl staining results of RGCs at 6 weeks after myopia induction in NC, LIM, DMSO, Que-L, Que-M, Que-H group (***P < 0.001, *P < 0.05). glycolysis is absorbed by neurons as a major energy source, suggesting that neurons upregulate glycolysis under stimulation [45].”
InfluentialActivity-dependent protein synthesis in neurons requires microglial-metabolic coupling
Adler, D. I., Martín‐Ávila, A., Cheng, E., Oliveira, M. M., Zhang, M., Evans, H. T., Yuan, D., Sam, R., Zhang, N., Sellés, M. C., et al. (2026) · Cell Metabolism · doi:10.1016/j.cmet.2026.05.006 · Cited by 7
Metabolic Plasticity in Developing and Aging Brain
Salmina, A. B. (2023) · Neurochemical Journal · doi:10.1134/s1819712423030157 · Cited by 6
Metabolic response of auditory brainstem neurons to their broad physiological activity range
Palandt, N., Resch, C., Unterlechner, P., Voshagen, L., Winhart, V. R., & Kunz, L. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16091 · Cited by 5
“This might hold especially for cellular compartments devoid of mitochondria, in which ATP is produced by glycolysis (Barros et al., 2021; Dienel, 2019; Yellen, 2018).”
BackgroundSulfide catabolism in hibernation and neuroprotection
Ichinose, F., & Hindle, A. G. (2024) · Nitric Oxide · doi:10.1016/j.niox.2024.03.002 · Cited by 5
Trease, A. J., Totusek, S., Lichter, E. Z., Stauch, K. L., & Fox, H. S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126441 · Cited by 5
Axo-vascular coupling mediated by oligodendrocytesPreprint
Restrepo, A., Trevisiol, A., Restrepo-Arango, C., Depp, C., Sasmita, A. O., Keller, A., Tzvetanova, I. D., Hirrlinger, J., & Nave, K. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.16.495900 · Cited by 6
“…glucose uptake, lactate production, and a metabolite flux between these two cells to support synaptic ATP production (Bak et al., 2009; Chuquet et al., 2010; Díaz-García et al., 2021; Dienel, 2012; Kasischke et al., 2004; Kasparov, 2016; Nehlig et al., 2004; Rouach et al., 2008; Yellen, 2018).”
BackgroundAn Overview of Oligodendrocyte Metabolism
Han, Q., & Cheng, J. (2025) · Advances in neurobiology · doi:10.1007/978-3-031-87919-7_7 · Cited by 5
Activity-dependent citrate dynamics in neurons
Rosen, P. C., Fu, P., Ferrán, B., Kim, E. E., Brooks, D. J., Lim, D., Díaz‐García, C. M., & Yellen, G. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2519902122 · Cited by 4
“We focused on neuronal glycolysis, which is triggered rapidly in response to depolarization ( 1 , 14 , 15 ).”
InfluentialSelf-citationPersistent adaptation through dual-timescale regulation of ion channel properties
Mondal, Y., Calabrese, R. L., & Marder, E. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2530340123 · Cited by 3
“Actually, in biological neurons, excitability arises from a richer interplay of mechanisms—for instance specialized channels that support rapid firing (33) or metabolic feedbacks that couple activity to cellular energy use (34).”
Wang, Z., Zhao, C., Xu, S., Zhao, M., McCracken, S., Apte, R. S., & Williams, P. R. (2026) · Nature Communications · doi:10.1038/s41467-026-71106-7 · Cited by 5
“Furthermore, the complement ofvasculature,glia,andinterstitial fl uidcompositionintheretinalikely creates a metabolic microenvironment dif fi cult to faithfully recapitulate ex vivo 38 .”
de Siqueira, D. V. F., Boaretto, N., & Leão, R. M. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.11.052 · Cited by 4
Xu, M., Zhang, X., Yu, X., Ma, C., Li, X., Chen, G., Yuan, G., Lin, S., & Cui, R. (2025) · Frontiers in Genetics · doi:10.3389/fgene.2025.1666561 · Cited by 6
“…while metabolites such as lactate, succinate, and α - ketoglutarate directly in fl uence epigenetic enzyme activity, and the availability of universal donors like S-adenosylmethionine (SAM) and Acetyl-CoA links metabolic status directly back to epigenetic potential (Yu and Li, 2024; Yellen, 2018).”
Park, E., Jin, S.-W., Lim, H.-J., Kim, H.-Y., Kang, M.-S., & Yang, S. (2021) · Toxics · doi:10.3390/toxics9070150 · Cited by 4
“Elevated ADP and calcium ion concentrations are central signals that contribute to this process, and ADP and calcium ions can depolarize the mitochondrial membrane potential [42].”
BackgroundMetabolic Plasticity of a Developing and Aging Brain
Salmina, A. B. (2023) · Нейрохимия · doi:10.31857/s1027813323030159 · Cited by 4
Haddad, J., Demirdelen, S., Barnes, C. E., et al. (2024) · Molecular Imaging · doi:10.1177/15353508241280573 · Cited by 4
“15,16 To this end, we performed sequential immuno fl uorescent staining for CD68 and α -SMA followed by in situ enzyme histochemistry of the same tissue sections to allow for their co-registration (Figure 2A).”
Role of cystathionine-β-synthase and hydrogen sulfide in down syndrome
Szabó, C. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00584 · Cited by 4
“In the brain, neurons are highly dependent on oxidative phosphorylation, while glial cells predominantly utilize glycolysis [157 – 160].”
Neuromodulatory control of energy reserves in dopaminergic neurons
Pulido, C., Gentry, M. S., & Ryan, T. A. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2523019122 · Cited by 3
“Recent quantitative evidence, however, does not support the idea that astrocytes, as a rule, provide lactate during or after electrical activity to support neuronal function ( 10 , 11 ).”
A proteomic signature for CNS adaptations to the valence of environmental stimulation
Shaw, A., Arnold, L. D., Privitera, L., Whitfield, P. D., Doherty, M. K., & Morè, L. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112515 · Cited by 4
“However, metabolic regulation of mitochondrial ATP production lies central to neuronal and glial function and processes related to neurotransmission [42-44].”
BackgroundZyśk, M., Pikuł, P., Kowalski, R. G., Lewandowski, K. C., Sakowicz‐Burkiewicz, M., & Pawełczyk, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228541 · Cited by 4
CMT disease 2A and demyelination decouple ATP and ROS production by axonal mitochondriaPreprint
van Hameren, G., Campbell, G. R., Deck, M., Berthelot, J., Chrast, R., & Tricaud, N. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/462523 · Cited by 2
“Nevertheless, the electrical isolation of the axon and the formation of the node of Ranvier is not the only function of the myelin sheath as it also largely participates to the metabolic homeostasis of the axon through the lactate shuttle process [75,76].”
BackgroundYang, X., Ha, G., & Needleman, D. J. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.20.392225 · Cited by 5
The neurobiology of love and addiction: Central nervous system signaling and energy metabolism
Esch, T., & Stefano, G. B. (2025) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-025-01333-w · Cited by 6
“This reciprocal relationship suggests that energy metabolism is not only a substrate for brain activity but also a critical modulator of the brain’s functional connectivity (Attwell & Laughlin, 2001; Buzsáki & Draguhn, 2004; Fries, 2005; Kann et al., 2014; Yellen, 2018).”
Dontiboina, H. R., Yadava, S., Nakka, V. P., Dumala, N., Viswanadh, M. K., Guntupalli, C., Nalluri, B. N., Malothu, N., Yadagiri, G., Gujjari, L., et al. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05967-w · Cited by 3
“Firstly, neurons in the brain are highly dependent on oxidative phosphorylation for ATP production and have limited capacity to utilize alternative energy sources such as glycolysis [246].”
Fan, Z., Liu, X., Gao, W., Zhang, L., Yang, X., & Li, J. (2024) · Food Science and Human Wellness · doi:10.26599/fshw.2024.9250275 · Cited by 3
Intracellular lactate dynamics in Drosophila neurons
Price, M. S., Rastegari, E., Gupta, R., Vo, K., Moore, T. I., & Venkatachalam, K. (2025) · iScience · doi:10.1016/j.isci.2025.113462 · Cited by 5
The interaction between resilience framework and neuron-astrocyte-synapse dynamics in AD
Ma, H., Zhao, H., Feng, X., & Gao, F. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1644532 · Cited by 4
“L-lactate can provide energy support for neurons and is an important fuel source for them (Yellen, 2018; Fink et al., 2021; Rae et al., 2024).”
Béland-Millar, A., & Messier, C. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.732242 · Cited by 4
“Importantly, the type of cell producing this lactate has been extensively debated (Díaz-García and Yellen, 2018; Fernández-Moncada et al., 2018; Yellen, 2018), and it is unclear if this lactate is shuttled out of the cell as waste product or shuttled out of the astrocytes as a potential energy…”
BackgroundKolotyeva, N. A., Gilmiyarova, F. N., Сергеевич, А. А., Baranich, T. I., Rozanova, N. A., Kukla, M. V., Tregub, P. P., & Salmina, A. B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914709 · Cited by 3
“…depend on mitochondria to support extensive synaptic activity and are able to transfer mitochondria along their dendrites to the peri-synaptic area [104,105]; however, some data suggest that neurons may utilize glucose and activate glycolysis for lactate overproduction upon their stimulation [106].”
BackgroundBarbosa, P. S. Z., Murat, C., & Leão, R. M. (2024) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-024-10037-8 · Cited by 3
“Given that neurons rely on oxidative phosphorylation in mitochondria to produce ATP from glucose (Yellen 2018), we then decided to test if inhibition of mitochondrial ATP production would reproduce the effects of low glu - cose.”
Boehm‐Sturm, P., Schuenke, P., Foddis, M., et al. (2025) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x251355049 · Cited by 3
Modeling the effect of cerebral capillary blood flow on neuronal firing
Chen, L., Hannawi, Y., & Terman, D. H. (2022) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2022.111018 · Cited by 3
Dugan, G., Akula, N., Marenco, S., Auluck, P. K., Raznahan, A., Liu, S., DeCasien, A. R., Xu, Q., Feng, N., Kolachana, B. S., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.19.613680 · Cited by 3
Neuronal Synaptic Communication and Mitochondrial Energetics in Human Health and Disease
Glausier, J. R. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-89525-8_5 · Cited by 2
Stress and high fat diet reconfigure the active translatome of CeA-NPY neurons
Ip, C. K., Zhang, L., Tasan, R. O., & Herzog, H. (2025) · Molecular Metabolism · doi:10.1016/j.molmet.2025.102176 · Cited by 2
Cai, L., Liu, Y., Tang, S., et al. (2025) · The FASEB Journal · doi:10.1096/fj.202500823r · Cited by 2
“Recently, a shift from oxidative phosphorylation to glycolysis has been linked to the pathology of PD [9].”
Central cytometabolic functional vascular coupling in health and disease
Sims, S. L., Lu, T., Weiss, B. E., Lin, R., Galopin, L. B., Wright, N. A., Norris, C. M., & Thibault, O. (2025) · npj Metabolic Health and Disease · doi:10.1038/s44324-025-00090-1 · Cited by 2
“However, thismodel has been challenged in recent years, with evidence indicating that the ANLSH is not well translated to in vivo settings or during stimulation 39 .”
An Emerging Role for OGDHL: From Mitochondrial Energy Metabolism to Neurodevelopmental Disorders
Liu, X., Zhang, G., Yu, D., & Han, J. (2025) · Biology · doi:10.3390/biology14121777 · Cited by 2
“Mitochondrial metabolism serves as the main energy source, providing ~93% of the total ATP used by neurons [2,3].”
Missaglia, M., Filippi, M., Esposito, F., & Giordano, A. (2026) · Acta Neuropathologica · doi:10.1007/s00401-026-03021-6 · Cited by 2
Physical Exercise Counteracts Impaired Cognition by Improving Mitochondrial Function
Maciel, P., Lamas, C. B., Araújo, A. C., Chagas, E. F. B., Guiguer, É. L., Curi, R., Pithon‐Curi, T. C., Almeida, M. C. D. S., Sloam, K. C. P., Sloan, L. A., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27104337 · Cited by 3
Brain mitochondria as key drivers of cognition and behaviour
Sandi, C., Lobo, M. K., Hollis, F., Hirabayashi, Y., de Juan‐Sanz, J., & Bolaños, J. P. (2026) · Nature reviews. Neuroscience · doi:10.1038/s41583-026-01061-1 · Cited by 5
“…stimulation can increase glycolytic flux within neurons rather than requiring lactate uptake from astrocytes as an obligatory substrate source 43,176 ; conversely, external lactate can reduce neuronal glucose consumption, suggesting flexible substrate selection rather than a single obligatory…”
Metabolic Plasticity of Astrocytes
Gorina, Y. V., Salmina, A. B., Erofeev, A. I., Can, Z., Bolshakova, A. V., Balaban, P. M., Борисович, Б. И., & Власова, О. Л. (2021) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093021060016 · Cited by 2
Li, H., Lin, S., Qi, P., Wang, J., Fan, M., Hongwei, H., Dong, Z., Xu, K., & Guo, B. (2022) · Frontiers in Marine Science · doi:10.3389/fmars.2022.995691 · Cited by 3
“…and secretion, cell growth and so on. frontiersin.org Glycolysis is one of the most ancient metabolic pathways for energy production in living cells (Yellen, 2018) and a primitive metabolic pathway that is easily exploited by cancer cells for energy to grow and spread (Fadaka et al., 2017).”
BackgroundVariable bioenergetic sensitivity of neurons and astrocytes to insulin and extracellular glucose
Sims, S. L., Frazier, H. N., Case, S. L., Lin, R., Trosper, J. N., Vekaria, H. J., Sullivan, P. G., & Thibault, O. (2024) · npj Metabolic Health and Disease · doi:10.1038/s44324-024-00037-y · Cited by 2
González‐Gutiérrez, A., Gaete, J., Esparza, A., Ibacache, A., Contreras, E. G., & Sierralta, J. A. (2025) · Glia · doi:10.1002/glia.70021 · Cited by 3
“Although the systemic response to starvation enables the survival of Drosophila animals, the adaptive mechanisms are insufficient to allow larvae to continue growing and reach the standard size of key organs, including the brain (Cheng et al. 2011; Contreras et al. 2021, 2018).”
Mapping of neurovascular and neurometabolic couplings by multimodal optical imaging
Hermán, P., Sanggaard, S., James, S., Akif, A., Mishra, S. K., Sanganahalli, B. G., Verhagen, J. V., Blumenfeld, H., & Hyder, F. (2025) · Cerebral Cortex · doi:10.1093/cercor/bhaf165 · Cited by 2
Gray, J., Halemirle, G., Ferrán, B., Rose, H., Redwine, T. L., Pham, S., Hagy, B., Pranay, A., Giorgione, J. R., Hussong, S. A., et al. (2025) · The Journal of Physiology · doi:10.1113/jp287618 · Cited by 2
Effect of Diet as a Factor of Exposome on Brain Function
Fedotova, A., Tiaglik, A. B., & Semyanov, A. V. (2021) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093021030108 · Cited by 2
Aoyama, B. B., Zanetti, G. G., Dias, E. V., Athié, M. C. P., Lopes‐Cendes, Í., & Vieira, A. S. (2022) · Hippocampus · doi:10.1002/hipo.23417 · Cited by 2
“These participate in both astrocytes and neuron glycolysis pathways (Yellen, 2018).”
BackgroundDe, T. D., Sharma, P., Tevatiya, S., Chauhan, C., Kumari, S., Singla, D., Srivastava, V., Rani, J., Hasija, Y., Pandey, K. C., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/774430 · Cited by 2
“To perform this action, a continuous neuronal stimulation is required, which consequently increases the energy demand of the brain [72,74].”
BackgroundAngireddy, R., Karisetty, B. C., Katsura, K. A., Diaz‐Rosado, A., Murali, S., Smith, S. M., Ohl, L., Clark, K., Kossenkov, A. V., & Bhoj, E. J. K. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.30.621078 · Cited by 2
“Anterograde and retrograde transport requires ATP, thus mitochondrial oxidative phosphorylation and mitochondrial-health play a critical role in neuronal homeostasis 38 .”
Song, J., Kang, J., Zhang, Y., Wang, Y., Yang, R. X., & Ning, B. (2025) · Medicinal Research Reviews · doi:10.1002/med.22103 · Cited by 1
“The lactate produced by astrocytes is thought to be transported to neurons through a model called astrocyte ‐ to ‐ neuron lactate shuttle (ANLS) [56].”
Zimbone, S., Battiato, G., Nibali, S. C., Николаевна, Н. И., Pesce, N. A., Pinto, V. D., Messina, A. A., Magrì, A., Tomasello, M. F., & Grasso, G. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05213-9 · Cited by 2
“Neurons, with their limited glycolytic capacity [63, 64], must rely on efficient OXPHOS, a process vulnerable to uncoupling-induced heat/ROS in neurodegeneration [62, 65].”
Modulation of neuronal firing modes by electric fields in a thermosensitive FitzHugh-Nagumo model
Nguessap, E. L. F., Roque, A. C., & Ferreira, F. F. (2025) · Nonlinear Dynamics · doi:10.1007/s11071-025-11906-6 · Cited by 1
Modelling brain metabolism with interacting nonautonomous phase oscillators
Barnes, S. J. K., Echeverría, A., Hawley, J., Suprunenko, Y. F., & Stefanovska, A. (2026) · Frontiers in Network Physiology · doi:10.3389/fnetp.2026.1720336 · Cited by 1
“The neurovascular unit is a highly nonautonomous system that adapts dynamically to meet fluctuating energy demands (Yellen, 2018; McConnell and Mishra, 2022).”
Wang, Y., Feng, C., Hou, Z., Liu, P., Xu, C., Chen, X., Li, Z., Xiao, Y., Li, X., Zhu, X., et al. (2026) · Bioactive Materials · doi:10.1016/j.bioactmat.2026.02.037 · Cited by 1
“Compared to oxidative phosphorylation, glycolysis generates ATP at a faster rate but with lower efficiency [95], resulting in a significant decrease in intra-cellular ATP levels.”
Alhathli, E. M., Cooper‐Knock, J., Girach, Z.-U.-A., Julian, T. H., Bauer, C. S., Timmons, H. O., Ward, B. D., Walker, H., Azzouz, M., Elrayess, M. A., et al. (2026) · BMC Medicine · doi:10.1186/s12916-026-04727-w · Cited by 3
A Flawed Conjecture Keeps Haunting Brain Energy Metabolism Research
Schurr, A. (2026) · NeuroSci · doi:10.3390/neurosci7030049 · Cited by 3
“In an article titled “Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism” [37], the author defined glycolysis as the partial metabolism of glucose to pyruvate or lactate that occurs in the cytosol (and that possibly is sub-compartmented within the…”
Metadata
- Authors
- Yellen, G.
- Affiliations
- Harvard University (US)
- Corresponding author
- Yellen, Gary
- ORCID
- Yellen, Gary
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2018-05-11
- Volume
- 217
- Issue
- 7
- Pages
- 2235-2246
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC6028533
- OpenAlex
- W2801615083
- Semantic Scholar
- ff7241917ffdf6751decf262f5a2edcbd2217b86
- Cited by
- 371
- References
- 131
- Citations by year
- 2026: 39 · 2025: 46 · 2024: 46 · 2023: 55 · 2022: 49 · 2021: 54 · 2020: 42 · 2019: 28 · 2018: 12
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01 NS055031, DP1 EB016985, R01 NS102586, R01 GM124038)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- neuronal energy metabolism, aerobic glycolysis, mitochondrial uncoupling, brain energy demand, lactate metabolism, calcium signaling
- MeSH terms
- Adenosine Diphosphate, Animals, Astrocytes, Brain, Calcium, Energy Metabolism, Glucose, Glycolysis, Humans, Neurons, Oxidative Phosphorylation, Lactic Acid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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