Illuminating spatial dynamics of glutamine metabolism with a sensitive genetically encoded biosensor

Area of Science:

• Cell Biology
• Metabolic Engineering
• Biochemistry

Background:

• Glutamine is a vital serum amino acid crucial for cellular functions like protein synthesis, energy production, and redox balance.
• Understanding the compartmentalized dynamics of glutamine metabolism within cells and across organelles remains a significant challenge in cell biology.

Purpose of the Study:

• To develop a novel tool for visualizing and quantifying intracellular glutamine dynamics with high spatiotemporal resolution.
• To investigate the interplay between glucose and glutamine metabolism in maintaining cellular energy homeostasis.

Main Methods:

• Development of a genetically encoded green fluorescent protein-based biosensor, termed iGlo, for intracellular glutamine detection.
• Utilizing iGlo for sensitive and specific measurement of glutamine uptake, production, and consumption in various cell types.
• Performing multiplexed imaging of iGlo with a lactate biosensor to analyze metabolic crosstalk in single cells.

Main Results:

• The iGlo biosensor demonstrated high sensitivity and specificity for glutamine.
• iGlo enabled real-time, high-resolution monitoring of glutamine dynamics across subcellular compartments and individual cells.
• Multiplexed imaging revealed the temporal coordination between glucose and glutamine metabolism for energy balance.

Conclusions:

• iGlo is a powerful and versatile tool for studying compartmentalized glutamine metabolism.
• This biosensor significantly advances the ability to investigate the spatiotemporal regulation of cellular metabolism.
• The findings provide new insights into how cells manage nutrient utilization for energy homeostasis.