Potassium ions promote hexokinase-II dependent glycolysis

• DOI: 10.1016/j.isci.2021.102346
• Publication Date: 2021-03-23T10:01:35Z
• Authors: Helmut Bischof; Sandra Burgstaller; Anna Springer; Lucas Matt; Thomas Rauter; Olaf A. Bachkönig; Tony Schmidt; Klaus Groschner; Rainer Schindl; Tobias Madl; Nikolaus Plesnila; Robert Lukowski; Wolfgang F. Graier; Roland Malli
• Keywords: Hexokinase; Adenosine triphosphate; Anaerobic glycolysis; HEK 293 cells; Bioenergetics

High expression levels of mitochondria-associated hexokinase-II (HKII) represent a hallmark metabolically highly active cells such as fast proliferating cancer cells. Typically, the enzyme provides crucial metabolic switch towards aerobic glycolysis. By imaging activities on single-cell level with genetically encoded fluorescent biosensors, we here demonstrate that HKII activity requires intracellular K+. The K+ dependency glycolysis in expressing was confirmed cell populations using extracellular flux analysis and nuclear magnetic resonance-based metabolomics. Reductions by gramicidin acutely disrupted HKII-dependent triggered energy stress pathways, while re-addition promptly restored glycolysis-dependent adenosine-5'-triphosphate generation. Moreover, activation KV1.3, voltage-gated channel, lowered cellular content glycolytic HEK293 Our findings unveil an essential cofactor provide mechanistic link between distinct channels metabolism.