Zhan Huiwang, Pal Dhiman Sankar, Borleis Jane, Deng Yu, Long Yu, Janetopoulos Chris, Huang Chuan-Hsiang, Devreotes Peter N
Department of Cell Biology and Center for Cell Dynamics, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Total Experience Learning, Alvernia University, Reading, PA, USA.
Nat Commun. 2025 Jul 1;16(1):5563. doi: 10.1038/s41467-025-60596-6.
Although glycolysis is traditionally considered a cytosolic reaction, here we show that glycolytic enzymes propagate as self-organized waves on the membrane/cortex of human cells. Altering these waves led to corresponding changes in glycolytic activity, ATP production, and dynamic cell behaviors, impacting energy-intensive processes such as macropinocytosis and protein synthesis. Mitochondria were absent from the waves, and inhibiting oxidative phosphorylation (OXPHOS) had minimal effect on ATP levels or cellular dynamics. Synthetic membrane recruitment of individual glycolytic enzymes increased cell motility and co-recruited additional enzymes, suggesting assembly of glycolytic multi-enzyme complexes in the waves. Remarkably, wave activity and glycolytic ATP levels increased in parallel across human mammary epithelial and other cancer cell lines with higher metastatic potential. Cells with stronger wave activity relied more on glycolysis than on OXPHOS for ATP. These results reveal a distinct subcellular compartment for enriched local glycolysis at the cell periphery and suggest a mechanism that coordinates energy production with cellular state, potentially explaining the Warburg effect.
虽然糖酵解传统上被认为是一种胞质反应，但我们在此表明，糖酵解酶以自组织波的形式在人类细胞的膜/皮质上传播。改变这些波会导致糖酵解活性、ATP产生和细胞动态行为的相应变化，影响诸如巨胞饮作用和蛋白质合成等能量密集型过程。波中不存在线粒体，抑制氧化磷酸化（OXPHOS）对ATP水平或细胞动态的影响极小。单个糖酵解酶的合成膜募集增加了细胞运动性，并共同募集了其他酶，这表明波中存在糖酵解多酶复合物的组装。值得注意的是，在具有较高转移潜能的人类乳腺上皮细胞和其他癌细胞系中，波活性和糖酵解ATP水平平行增加。波活性较强的细胞在产生ATP方面更多地依赖糖酵解而非OXPHOS。这些结果揭示了细胞周边存在一个用于富集局部糖酵解的独特亚细胞区室，并提出了一种将能量产生与细胞状态相协调的机制，这可能解释了瓦伯格效应。
