Sulfate starvation response modules connect sulfur metabolism to photorespiration and photosynthesis

Mineral nutrients are essential for plant growth and development. Sulfur (S), as a macronutrient, is incorporated into numerous critical S-containing metabolites that play key roles in mitigating both abiotic and biotic stresses. Understanding how plants regulate S homeostasis and integrate it with other physiological processes is crucial for developing crops that can better withstand environmental challenges. Here, we demonstrate that the conserved sulfate starvation transcriptional response across Arabidopsis, tomato, rice, and Setaria is limited to only seven genes. We further characterize the roles of two of these genes, PYD4 (PYRIMIDINE 4) and MGL (METHIONINE GAMMA-LYASE), in S metabolite regulation and the sulfate starvation response. Our genetic and biochemical analyses show that PYD4 is embedded within the S starvation network, positively regulating transcript levels of key S-marker genes, including four of the seven conserved genes across these species, and serving as an integrator of S metabolism and photorespiration. MGL also positively regulates S-marker genes, while additionally modulating diverse processes under sulfate starvation, such as photosynthesis and oxidoreductase homeostasis. Notably, MGL-deficient lines fail to respond adequately to sulfate starvation and exhibit impaired mechanisms for maintaining photosynthetic efficiency. Overall, our findings indicate that the S starvation response is deeply embedded within primary plant metabolism. Disruption of its regulators alters metabolism at multiple levels, affecting traits central to crop improvement, such as photorespiration and photosynthesis.