Wei, Yao; Miao, QianQian; Zhang, Qian; Mao, Shiyu; Li, Mengke; Xu, Xing; Xia, Xian; Wei, Ke; Fan, Yu; Zheng, Xinlei

DOI: PMID:

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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