2. Academic Validation
  3. Aerobic glycolysis is the predominant means of glucose metabolism in neuronal somata, which protects against oxidative damage

Aerobic glycolysis is the predominant means of glucose metabolism in neuronal somata, which protects against oxidative damage

  • Nat Neurosci. 2023 Nov 23. doi: 10.1038/s41593-023-01476-4.
Yao Wei # 1,  QianQian Miao # 2,  Qian Zhang # 1,  Shiyu Mao 2,  Mengke Li 1,  Xing Xu 1,  Xian Xia 1,  Ke Wei 1,  Yu Fan 1,  Xinlei Zheng 1,  Yinquan Fang 2,  Meng Mei 1,  Qingyu Zhang 1,  Jianhua Ding 2,  Yi Fan 2,  Ming Lu 2,  Gang Hu 3 4
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
  • 2 Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, China.
  • 3 Department of Pharmacology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China. ghu@njmu.edu.cn.
  • 4 Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, China. ghu@njmu.edu.cn.
  • # Contributed equally.
PMID: 37996529 DOI: 10.1038/s41593-023-01476-4
Abstract

It is generally thought that under basal conditions, neurons produce ATP mainly through mitochondrial oxidative phosphorylation (OXPHOS), and glycolytic activity only predominates when neurons are activated and need to meet higher energy demands. However, it remains unknown whether there are differences in glucose metabolism between neuronal somata and axon terminals. Here, we demonstrated that neuronal somata perform higher levels of aerobic glycolysis and lower levels of OXPHOS than terminals, both during basal and activated states. We found that the glycolytic enzyme Pyruvate Kinase 2 (PKM2) is localized predominantly in the somata rather than in the terminals. Deletion of Pkm2 in mice results in a switch from aerobic glycolysis to OXPHOS in neuronal somata, leading to oxidative damage and progressive loss of dopaminergic neurons. Our findings update the conventional view that neurons uniformly use OXPHOS under basal conditions and highlight the important role of somatic aerobic glycolysis in maintaining antioxidant capacity.

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