Revealing the spatiotemporal dynamics of methionine metabolism with a genetically encoded single-fluorophore biosensor

Abstract

Methionine is an essential amino acid, used for protein synthesis, redox homeostasis, and methylation reactions throughout the cell. However, the compartmentalized dynamics of methionine have remained elusive, due to a lack of available tools to measure methionine with high spatial and temporal resolution. To address this limitation, we have developed a single fluorescent protein-based methionine optical reporter (Meteor) which reports subcellular changes in methionine with high dynamic range. Using Meteor, we demonstrate the subcellular uptake of methionine in multiple cell lines into several locations, including the mitochondrial matrix. Furthermore, we use Meteor to illuminate the dynamics of the methionine cycle in the cytoplasm and nucleus, finding cancer cells can rapidly increase methionine from metabolic precursors in both locations. Finally, demonstrated that Meteor can be used to visualize methionine dynamics in vivo using Caenorhabditis elegans. Thus, we have developed a new tool to measure methionine dynamics across scales with high dynamic range and spatiotemporal resolution.