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Cell-specific expression of key mitochondrial enzymes limits OXPHOS in astrocytes of the adult human neocortex and hippocampal formation

Lookup NU author(s): Dr Chun ChenORCiD, Professor Gavin Hudson

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© The Author(s) 2024.The astrocyte-to-neuron lactate shuttle model entails that, upon glutamatergic neurotransmission, glycolytically derived pyruvate in astrocytes is mainly converted to lactate instead of being entirely catabolized in mitochondria. The mechanism of this metabolic rewiring and its occurrence in human brain are unclear. Here by using immunohistochemistry (4 brains) and imaging mass cytometry (8 brains) we show that astrocytes of the adult human neocortex and hippocampal formation express barely detectable amounts of mitochondrial proteins critical for performing oxidative phosphorylation (OXPHOS). These data are corroborated by queries of transcriptomes (107 brains) of neuronal versus non-neuronal cells fetched from the Allen Institute for Brain Science for genes coding for a much larger repertoire of entities contributing to OXPHOS, showing that human non-neuronal elements barely expressed mRNAs coding for such proteins. With less OXPHOS, human brain astrocytes are thus bound to produce more lactate to avoid interruption of glycolysis. (Figure presented.)

Publication metadata

Author(s): Dobolyi A, Cservenak M, Bago AG, Chen C, Stepanova A, Paal K, Lee J, Palkovits M, Hudson G, Chinopoulos C

Publication type: Article

Publication status: Published

Journal: Communications Biology

Year: 2024

Volume: 7

Issue: 1

Online publication date: 24/08/2024

Acceptance date: 16/08/2024

Date deposited: 02/09/2024

ISSN (electronic): 2399-3642

Publisher: Nature Research

URL: https://doi.org/10.1038/s42003-024-06751-z

DOI: 10.1038/s42003-024-06751-z

Data Access Statement: All data have been deposited at Mendeley (https://doi.org/10.17632/wj3ndgbchf.1)67. Source data are provided in Supplementary Data 1. All other data are also available through the corresponding author (Christos Chinopoulos) on reasonable request.

PubMed id: 39181993

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