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This research aims to understand how mitochondrial dysfunction affects the metabolism of different neural cell types.

May 17, 2026Open Access

Quantitative proteomic profiling of neural cells-specific metabolic reprogramming in response to mitochondrial dysfunction using iMPAQT2

Key Points

This research aims to understand how mitochondrial dysfunction affects the metabolism of different neural cell types.
Utilized the iMPAQT2 proteomics platform to analyze metabolic profiles of neurons, oligodendrocytes, and astrocytes.
Induced mitochondrial dysfunction using inhibitors chloramphenicol and oligomycin while measuring metabolic shifts in cell types.
Compared expression levels of oxidative phosphorylation enzymes and metabolic pathways across the cell types.
Neurons and oligodendrocytes primarily rely on oxidative phosphorylation for ATP production, unlike astrocytes, which utilize glycolysis.
Oligodendrocytes showed major reductions in glycolysis and critical metabolic pathways due to mitochondrial inhibitors, particularly for cholesterol synthesis and fatty acid degradation.
The findings highlight oligodendrocytes' increased vulnerability to mitochondrial dysfunction, implicating metabolic reprogramming in neurodegenerative disease progression.

Abstract

Age-related mitochondrial dysfunction is increasingly recognized as a key contributor to neurodegenerative disease pathogenesis. In the central nervous system, neurons, oligodendrocytes, and astrocytes which derived from neural stem cells, fulfill distinct metabolic and functional roles. However, the specific vulnerabilities of these cell types to mitochondrial impairment remain unclear. In this study, we employed the iMPAQT2 proteomics platform to systematically compare the metabolic profiles of neurons, oligodendrocytes, and astrocytes, and to elucidate the molecular consequences of mitochondrial dysfunction induced by chloramphenicol and oligomycin. Our findings indicate that neurons and oligodendrocytes primarily rely on oxidative phosphorylation (OXPHOS) for ATP production, whereas astrocytes predominantly utilize glycolysis. It is noteworthy that oligodendrocytes exhibited enriched pathways for cholesterol synthesis, fatty acid degradation, and heme catabolism—processes that are critical for myelin maintenance. Treatment with the mitochondrial function inhibitors chloramphenicol or oligomycin reduced the expression of OXPHOS enzymes in all cell types. This reduction was particularly pronounced in oligodendrocytes for glycolysis, cholesterol synthesis, heme degradation, and fatty acid degradation. These results suggest that oligodendrocytes are particularly vulnerable to mitochondrial dysfunction, which may play a pivotal role in the pathogenesis of age-related neurodegenerative disorders.

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