Copper homeostasis: Crosstalk with plant secondary metabolism and stress responses.

Copper (Cu) is an essential micronutrient for plants that functioning as a cofactor in numerous enzymes. However, it becomes toxic in excess, necessitating homeostatic mechanisms. In this review, we synthesize current knowledge of the Cu uptake, transport, and homeostasis in plants, and examine the Cu-mediated regulation of plant secondary metabolism. This review outlines the forms of Cu present in soils and plant systems and describes how roots acquire Cu (predominantly as Cu²⁺, which is then reduced to Cu⁺ at the root surface) via high-affinity transporters. Within the plant, the Cu uptake and distribution are mediated by a network of membrane transporters, chaperones, and storage molecules. These components ensure an adequate supply to essential cuproproteins while preventing toxicity. Molecular regulatory mechanisms, notably the SQUAMOSA Promoter Binding Protein-Like 7 (SPL7) transcription factor and Cu-responsive microRNAs such as miR397, miR398, and miR408, regulate Cu concentration in plants and modulate gene expression to maintain homeostasis under fluctuating Cu availability. Cu availability significantly influences the secondary metabolite biosynthesis. As a cofactor of key enzymes such as polyphenol oxidases and laccases, Cu affects the production of phenolics (including lignin), flavonoids, and other defensive secondary metabolites. Adequate Cu nutrition thereby enhances plant defense responses by fortifying cell walls, supporting antioxidant enzymes, and promoting the synthesis of antimicrobial compounds. Finally, we highlight the practical applications of Cu management strategies, such as optimizing foliar Cu supplementation and breeding for Cu-efficient genotypes, to enhance stress resilience, yield stability, and the nutritional quality of crops.