Authors: Haoming Wang, John W. Vant, Andrew Zhang, Richard G. Sanchez, Youjun Wu, Mary L. Micou, Vincent Luczak, Zachary Whiddon, Natasha M. Carlson, Seungyoon B. Yu, Mirna Jabbo, Seokjun Yoon, Ahmed A. Abushawish, Majid Ghassemian, Takeya Masubuchi, Quan Gan, Shigeki Watanabe, Eric R. Griffis, Marc Hammarlund, Abhishek Singharoy and Gulcin Pekkurnaz
Nature Metabolism, 11 September 2024
Hexokinase 1 (HK1), the initial enzyme involved in glycolysis, is expressed specifically in highly metabolically active cells such as neurons. HK1 is localized to the outer mitochondrial membrane, suggesting a role in metabolism, but its impact is not fully understood. In this study, scientists investigate mechanisms underlying HK1 localization and activity regulation.
To assess the effects of HK1 O-GlcNAcylation on neural network activity in vitro in real time, the team used Axion BioSystems’ noninvasive Maestro MEA system. MEA recordings revealed that inhibition of HK1 O-GlcNAcylation reduced firing rate and network activity, suggesting a critical role of HK1 O-GlcNAcylation in helping neurons meet required metabolic demands. Together with other results, the authors conclude that the study “reveals a previously unappreciated pathway that links neuronal metabolism and mitochondrial function through OGT and the formation of the glycolytic metabolon, providing potential strategies for tackling metabolic and neurological disorders.”
