Fig. 3. Iron-loaded ferritin is secreted through extracellular vesicles under the regulation of IRP/IRE in CD63. CD63 is one of the exosomal markers. In iron excess conditions, not only an iron storage protein, ferritin, but also CD63 is induced. CD63 recruits nuclear receptor coactivator 4 (NCOA4) to pack iron-loaded ferritin to release as extracellular vesicles. Of note, CD63 gene was discovered to possess the IRE consensus sequence at the 5’ untranslated region of mRNA, similar to that of ferritin gene, which blocks the translation of CD63 in the presence of ample amount of iron under the IRE/IRP system. IRE, iron-responsive element; IRP, iron-regulatory protein. Refer to text and the reference [32] for details.

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