Chloroplast glutaredoxin S12 regulates photosynthesis and growth through redox modulation of SufB

Redox homeostasis and Fe-S protein maturation are critical for chloroplast function. Chloroplast-localized glutaredoxins (Grxs) are versatile enzymes that function either as oxidoreductases or Fe-S cluster transferases. However, their target proteins and underlying molecular mechanisms remain incompletely understood. Here, we demonstrate that the cysteine 34 within the active site motif of chloroplast-localized Arabidopsis GrxS12 is the key residue governing its oxidoreductase activity, while the C-terminal cysteine 92 plays a secondary role. These cysteines undergo glutathionylation or form an intramolecular disulfide bond, which can be reduced by Trx-m1. Although GrxS12 is unable to bind Fe-S clusters itself, it interacts with and reduces the Fe-S cluster assembly protein SufB, thereby regulating Fe-S protein maturation. Loss of GrxS12 induces redox alterations of multiple chloroplast proteins, increased oxidation of SufB, and decreased abundances of several Fe-S proteins. These changes likely underlie the observed structural damage to chloroplasts, reduced photosynthetic efficiency, and slower growth in grxs12 mutants. Our results reveal a novel mechanism by which GrxS12 regulates chloroplast Fe-S cluster biogenesis through its oxidoreductase activity.