Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Bischof, H; Burgstaller, S; Springer, A; Matt, L; Rauter, T; Bachkönig, OA; Schmidt, T; Groschner, K; Schindl, R; Madl, T; Plesnila, N; Lukowski, R; Graier, WF; Malli, R.
Potassium ions promote hexokinase-II dependent glycolysis.
iScience. 2021; 24(4): 102346-102346.
Doi: 10.1016/j.isci.2021.102346
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PubMed
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- Leading authors Med Uni Graz
- Bischof Helmut
- Malli Roland
- Co-authors Med Uni Graz
- Bachkönig Olaf Arne Georg
- Burgstaller Sandra
- Graier Wolfgang
- Groschner Klaus
- Madl Tobias
- Rauter Thomas
- Schindl Rainer
- Schmidt Tony
- Springer Anna Maria
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- 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 KV1.3, 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. © 2021 The Author(s).