2026-06-01 九州大学
＜関連情報＞
- https://www.kyushu-u.ac.jp/ja/researches/view/1493
- https://www.sciencedirect.com/science/article/pii/S1567724926000589
iMPAQT2を用いたミトコンドリア機能不全に対する神経細胞特異的代謝再プログラミングの定量的プロテオミクス解析 Quantitative proteomic profiling of neural cells-specific metabolic reprogramming in response to mitochondrial dysfunction using iMPAQT2
Akito Tani, Mikako Yagi, Natsuki Horiuchi, Kento Nagata, Tomohiro Tanaka, Hiroki Kittaka, Ko Igami, Takeshi Uchiumi
Mitochondrion Available online 14 May 2026
DOI:https://doi.org/10.1016/j.mito.2026.102168
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.
