The tradeoff between speed and sustainability: Investigating the cellular and translational response to 1-carbon metabolism perturbation

Abstract

Cells continuously monitor and respond to nutrient availability to maintain homeostasis and ensure survival. Nutrient sensing orchestrates a coordinated network of signaling, metabolic, and translational responses that enable adaptation to changing environments. Central to this process is one-carbon metabolism, which integrates cellular inputs to support nucleotide synthesis, redox balance, and methylation reactions. By providing substrates for methylation and other modification reactions, one-carbon metabolism serves as a key interface between metabolism and the regulation of transcription, translation, and protein function. The integration of metabolic and signaling cues shapes cell fate, enabling transitions between growth, quiescence, and differentiation. Nutrient-sensing pathways such as AMPK and mTOR convert metabolic information into coordinated control of biosynthetic processes, while posttranslational modifications act as rapid molecular responses that fine-tune protein activity and reinforce longer-term transcriptional and metabolic programs. Together, metabolic pathways, translation, and PTMs form an integrated system that enables precise control of cellular function during nutrient fluctuations. Disruption of these nutrient-sensing processes contributes to metabolic diseases, cancer, and developmental disorders. Understanding how one-carbon metabolism and translational control intersect to direct cellular adaptation will improve our understanding of nutrient sensing and cell fate outcomes.