Sortin1-Hypersensitive Mutants Link Vacuolar-Trafficking Defects and Flavonoid Metabolism in Arabidopsis Vegetative Tissues

SummarySortin1 is a chemical genetic-hit molecule that causes specific mislocalization of plant and yeast-soluble and membrane vacuolar markers. To better understand its mode of action, we designed a Sortin1-hypersensitive screen and identified several Sortin1-hypersensitive and flavonoid-defective mutants. Mechanistically, Sortin1 mimics the effect of the glutathione inhibitor buthionine sulfoximine and alters the vacuolar accumulation of flavonoids, likely blocking their transport through vacuole-localized ABC transporters. Structure-activity relationship studies conducted in Arabidopsis revealed the structural requirements for Sortin1 bioactivity and demonstrated that overlapping Sortin1 substructures can be used to discriminate between vacuolar-flavonoid accumulations and vacuolar-biogenesis defects. We conclude that Sortin1 is a valuable probe for dissecting novel links among flavonoid transport, vacuolar integrity, and the trafficking of vacuolar targeted cargoes in Arabidopsis.PaperClip To listen to this audio, enable JavaScript on your browser. However, you can download and play the audio by clicking on the icon belowHelp with MP3 filesOptionsDownload audio (5304 K)

► Flavonoid metabolism influences the fate of vacuolar-targeted cargoes in Arabidopsis ► Sortin1-hypersensitive mutants encode genes in flavonoid metabolism ► Sortin1 generates oxidative stress and mimics the effect of known glutathione inhibitors ► Chemical analyses provide topological information of the Sortin1-bioactive structures