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Post-translational modification is a critical mechanism by which trace mineral transporters rapidly adapt to their environment to homeostatically regulate ion transport. Recently, a novel pathway was described whereby iron stimulates the ubiquitination and proteasomal degradation of the trace mineral transporter ZIP14. Discovery of this pathway suggests the proteasome as a potential therapeutic target for regulation of iron storage. Moreover, these findings contribute to a theoretical framework that can be applied to other ubiquitinated trace mineral transporters. This review will detail the current state of knowledge regarding the ubiquitination of trace mineral transporters, focusing on iron and zinc transporters, and the potential utility of post-translational modification of trace mineral transporters in the treatment of disease.

Homeostatic regulation of trace mineral transport by ubiquitination of membrane transporters