RT Journal Article SR Electronic T1 Maintaining proton homeostasis is an essential role of glucose metabolism in cell survival JF bioRxiv FD Cold Spring Harbor Laboratory SP 058594 DO 10.1101/058594 A1 Yanfen Cui A1 Yuanyuan Wang A1 Pan Xing A1 Li Qiu A1 Miao Liu A1 Xin Wang A1 Guoguang Ying A1 Binghui Li YR 2016 UL http://biorxiv.org/content/early/2016/06/13/058594.abstract AB Aerobic glycolysis, termed “the Warburg Effect”, supports cell proliferation, and glucose deprivation directly elicits necrosis or shifts stimuli-induced apoptosis to necrosis. However, how glucose metabolism regulates cell survival or death choice remains largely unclear. Here we use our recently developed method to monitor in real-time cellular apoptosis and necrosis, and uncover a metabolic homeostasis linked to cell death control. We show that glucose metabolism is the major source to maintain both intracellular and extracellular proton homeostasis. Glucose deficiency leads to lack of proton provision, which provokes a compensatory lysosomal proton efflux and resultant increased lysosomal pH. This lysosomal alkalinization can trigger necrosis. Furthermore, artificial proton supplement enables cells to survive glucose deprivation. Taken together, our results reveal a critical role of glucose metabolism in maintaining cellular microenvironment, and provide a better understanding of the essential requirement of aerobic glycolysis for proliferating cells whose active anabolism consumes a great many protons.