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标题：Potassium ions promote hexokinase-II dependent glycolysis
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作者：Helmut Bischof ; Sandra Burgstaller ; Anna Springer 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：4
页码：1-36
DOI：10.1016/j.isci.2021.102346
语种：English
出版社：Elsevier
摘要：SummaryHigh 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.Graphical abstractDisplay OmittedHighlights•HKII expression sensitizes cellular metabolism for intracellular K•Intracellular K+depletion abates the metabolic activity of HKII-positive cells•(Re-)elevations of intracellular K+restore glycolysisHere, Bischof et al. report that the activity of hexokinase-II requires a high intracellular K+concentration. Cells that rely on hexokinase-II activity for augmented aerobic glycolysis are thus vulnerable to intracellular K+depletion.