Elucidating the spatiotemporal dynamics of glucose metabolism with genetically encoded fluorescent biosensors

Glucose metabolism has been well understood for many years, but some intriguing questions remain regarding the subcellular distribution, transport, and functions of glycolytic metabolites. To address these issues, a living cell metabolic monitoring technology with high spatiotemporal resolution is needed. Genetically encoded fluorescent sensors can achieve specific, sensitive, and spatiotemporally resolved metabolic monitoring in living cells and in vivo, and dozens of glucose metabolite sensors have been developed recently. Here, we highlight the importance of tracking specific intermediate metabolites of glycolysis and glycolytic flux measurements, monitoring the spatiotemporal dynamics, and quantifying metabolite abundance. We then describe the working principles of fluorescent protein sensors and summarize the existing biosensors and their application in understanding glucose metabolism. Finally, we analyze the remaining challenges in developing high-quality biosensors and the huge potential of biosensor-based metabolic monitoring at multiple spatiotemporal scales.