2.B.71.  The Iron Transporting Hinokitiol (Hinokitiol) Family 

Deficiencies of the transmembrane iron-transporting protein ferroportin (FPN1) cause the iron misdistribution that underlies ferroportin disease, anemia of inflammation, and several other human diseases and conditions. A small molecular natural product, hinokitiol, is a surrogate transmembrane iron transporter that can restore hemoglobinization in zebrafish deficient in other iron transporting proteins and can increase gut iron absorption in FPN1-deficient flatiron mice. Hinokitiol redistributes iron from the liver to red blood cells in flatiron mice, thereby increasing hemoglobin and hematocrit (Ekaputri et al. 2022). Hinokitiol releases iron trapped within liver macrophages; hinokitiol-Fe complexes transfer iron to transferrin, and the resulting transferrin-Fe complexes drive red blood cell maturation in a transferrin-receptor-dependent manner. In FPN1-deficient primary macrophages derived from patients with ferroportin disease, hinokitiol moves labile iron from inside to outside cells and decreases intracellular ferritin levels (Ekaputri et al. 2022).

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