An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation
Recommended Citation
Suhail H, Nematullah M, Rashid F, Sajad M, Fatma M, Singh J, Zahoor I, Cheung WL, Tiwari N, Ayasolla K, Kumar A, Hoda N, Rattan R, and Giri S. An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation. iScience 2023; 26(10):107921.
Document Type
Article
Publication Date
10-20-2023
Publication Title
iScience
Abstract
Metabolism and energy processes governing oligodendrocyte function during neuroinflammatory disease are of great interest. However, how varied cellular environments affect oligodendrocyte activity during neuroinflammation is unknown. We demonstrate that activated microglial energy metabolism controls oligodendrocyte mitochondrial respiration and activity. Lipopolysaccharide/interferon gamma promote glycolysis and decrease mitochondrial respiration and myelin protein synthesis in rat brain glial cells. Enriched microglia showed an early burst in glycolysis. In microglia-conditioned medium, oligodendrocytes did not respire and expressed less myelin. SCENITH revealed metabolic derangement in microglia and O4-positive oligodendrocytes in endotoxemia and experimental autoimmune encephalitogenic models. The early burst of glycolysis in microglia was mediated by PDPK1 and protein kinase B/AKT signaling. We found that microglia-produced NO and itaconate, a tricarboxylic acid bifurcated metabolite, reduced mitochondrial respiration in oligodendrocytes. During inflammation, we discovered a signaling pathway in microglia that could be used as a therapeutic target to restore mitochondrial function in oligodendrocytes and induce remyelination.
PubMed ID
37841597
Volume
26
Issue
10
First Page
107921
Last Page
107921
