Sulfur in Dialogue with Phosphorus, Nitrogen, and Iron: Regulatory Networks in Plant Nutrient Homeostasis

Sulfur (S) is an essential macronutrient for plant growth and resilience. The S-amino acids cysteine (Cys) and methionine (Met) are indispensable for protein synthesis and structural integrity, as well as redox homeostasis and cofactor assembly. Over the past several decades, biochemical and molecular genetic studies demonstrated the core steps in sulfate (SO42-) uptake and assimilation pathways, while it has become increasingly evident that S homeostasis in plants cannot be understood in isolation. Robust and reciprocal regulatory interactions link S with phosphorus (P), nitrogen (N), and iron (Fe). Plants remodel membrane lipid compositions, replacing the phospholipids with sulfolipids under P deficiency. Cys/Met biosynthesis is coordinated with N metabolism. The Fe-S cluster assembly requires a balanced supply of Fe and S. These interactions are orchestrated through shared regulatory circuits and specific hub-regulatory transcription factors, including SULFUR LIMITATION 1 (SLIM1), PHOSPHATE STARVATION RESPONSE 1 (PHR1), NIN-LIKE PROTEIN 7 (NLP7), and FER-LIKE IRON DEFICIENCY-INDUCED FACTOR (FIT). Comparative studies reveal both species-specific and evolutionarily conserved regulatory networks. This review deliberately focuses on mechanistic insights into the regulatory circuits revealed from studies with the model plant Arabidopsis thaliana, where the genetic and molecular resolution enabled detailed dissection of the signaling and regulatory networks. This review also highlights unresolved mechanistic gaps and provides insights into systems-level understanding and potential translational approaches that can be implemented to improve crop nutrient use efficiency and stress resilience.