Intracellular Lactate Dynamics in Drosophila Neurons

Authors

Matthew S Price
Elham Rastegari
Richa Gupta
Katie Vo
Travis I Moore
Kartik Venkatachalam

Language

English

Publication Date

10-17-2025

Journal

iScience

DOI

10.1016/j.isci.2025.113462

PMID

41169509

PMCID

PMC12570357

PubMedCentral® Posted Date

8-28-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Rates of lactate production and consumption reflect the metabolic state of many cell types, including neurons. Here, we investigated the effects of nutrient deprivation on lactate dynamics in Drosophila neurons by leveraging the limiting effects of the unstirred layer, a diffusion barrier that forms around cells in culture. We found that neurons constitutively consume lactate when the availability of trehalose, a glucose disaccharide preferred by insects, is limited by the unstirred layer. Acute mechanical disruption of the unstirred layer reduced this reliance on lactate. Through kinetic modeling and experimental validation, we demonstrate that neuronal lactate consumption rates under unstirred layer conditions correlate inversely with the cells’ mitochondrial density. Furthermore, neuronal lactate levels exhibited temporal correlations that allowed postperturbation lactate dynamics to be predicted by preperturbation values. Collectively, our findings reveal the influence of naturally forming diffusion barriers on neuronal metabolic preferences and demonstrate the existence of temporal correlations between lactate dynamics under conditions of nutrient deprivation and those evoked by the subsequent restoration of nutrient availability.

Keywords

Rates of lactate production and consumption reflect the metabolic state of many cell types, including neurons. Here, we investigated the effects of nutrient deprivation on lactate dynamics in Drosophila neurons by leveraging the limiting effects of the unstirred layer, a diffusion barrier that forms around cells in culture. We found that neurons constitutively consume lactate when the availability of trehalose, a glucose disaccharide preferred by insects, is limited by the unstirred layer. Acute mechanical disruption of the unstirred layer reduced this reliance on lactate. Through kinetic modeling and experimental validation, we demonstrate that neuronal lactate consumption rates under unstirred layer conditions correlate inversely with the cells’ mitochondrial density. Furthermore, neuronal lactate levels exhibited temporal correlations that allowed postperturbation lactate dynamics to be predicted by preperturbation values. Collectively, our findings reveal the influence of naturally forming diffusion barriers on neuronal metabolic preferences and demonstrate the existence of temporal correlations between lactate dynamics under conditions of nutrient deprivation and those evoked by the subsequent restoration of nutrient availability.

Published Open-Access

yes

Recommended Citation

Price, Matthew S; Rastegari, Elham; Gupta, Richa; et al., "Intracellular Lactate Dynamics in Drosophila Neurons" (2025). Faculty, Staff and Student Publications. 6291.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6291