摘要
Glucose is one of major nutrients and its catabolism provides energy and/or building bricks for cell proliferation. Glucose deficiency results in cell death. However, the underlying mechanism still remains elusive. By using our recently developed method to monitor real-time cellular apoptosis and necrosis, we show that glucose deprivation can directly elicit necrosis, which is promoted by mito- chondrial impairment, depending on mitochondrial adenosine triphosphate （ATP） generation instead of ATP depletion. We demon- strate that glucose metabolism is the major source to produce protons. Glucose deficiency leads to lack of proton provision while mitochondda[ electron transfer chain continues consuming protons to generate energy, which provokes a compensatory lysosomal proton efflux and resultant increased lysosomal pH. This [ysosomal aikaUnization can trigger apoptosis or necrosis depending on the extent of alkalinization. Taken together, our results build up a metabolic connection between glycolysis, mitochondrion, and iysosome, and reveal an essential role of glucose metabolism in maintaining proton homeostasis to support cell survival.
