Potassium ions promote hexokinase-II dependent glycolysis

Bischof, Helmut; Burgstaller, Sandra; Springer, Anna; Matt, Lucas; Rauter, Thomas; Bachkoenig, Olaf A.; Schmidt, Tony; Groschner, Klaus; Schindl, Rainer; Madl, Tobias; Plesnila, Nikolaus; Lukowski, Robert; Graier, Wolfgang F. and Malli, Roland (2021): Potassium ions promote hexokinase-II dependent glycolysis. In: Iscience, Vol. 24, No. 4, 102346

Abstract

High expression levels of mitochondria-associated hexokinase-II (HKII) represent a hallmark of metabolically highly active cells such as fast proliferating cancer cells. Typically, the enzyme provides a crucial metabolic switch towards aerobic glycolysis. By imaging metabolic activities on the single-cell level with genetically encoded fluorescent biosensors, we here demonstrate that HKII activity requires intracellular K+. The K+ dependency of glycolysis in cells expressing HKII was confirmed in cell populations using extracellular flux analysis and nuclear magnetic resonance-based metabolomics. Reductions of intracellular K+ by gramicidin acutely disrupted HKII-dependent glycolysis and triggered energy stress pathways, while K+ re-addition promptly restored glycolysis-dependent adenosine-5'-triphosphate generation. Moreover, expression and activation of K(V)1.3, a voltage-gated K+ channel, lowered cellular K+ content and the glycolytic activity of HEK293 cells. Our findings unveil K+ as an essential cofactor of HKII and provide a mechanistic link between activities of distinct K+ channels and cell metabolism.

• Item Type: Journal article
• Faculties: Medicine; Medicine > Munich Cluster for Systems Neurology (SyNergy)
• Subjects: 600 Technology > 610 Medicine and health
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198