PUBLICATION

Restored iron transport by a small molecule promotes absorption and hemoglobinization in animals

Authors
Grillo, A.S., SantaMaria, A.M., Kafina, M.D., Cioffi, A.G., Huston, N.C., Han, M., Seo, Y.A., Yien, Y.Y., Nardone, C., Menon, A.V., Fan, J., Svoboda, D.C., Anderson, J.B., Hong, J.D., Nicolau, B.G., Subedi, K., Gewirth, A.A., Wessling-Resnick, M., Kim, J., Paw, B.H., Burke, M.D.
ID
ZDB-PUB-170513-3
Date
2017
Source
Science (New York, N.Y.)   356: 608-616 (Journal)
Registered Authors
Paw, Barry
Keywords
none
MeSH Terms
  • Animals
  • Caco-2 Cells
  • Gastrointestinal Absorption
  • Hemoglobins/metabolism
  • Humans
  • Iron/metabolism*
  • Iron-Binding Proteins/metabolism
  • Monoterpenes/metabolism
  • Rats
  • Saccharomyces cerevisiae/metabolism
  • Tropolone/analogs & derivatives
  • Tropolone/metabolism
PubMed
28495746 Full text @ Science
Abstract
Multiple human diseases ensue from a hereditary or acquired deficiency of iron-transporting protein function that diminishes transmembrane iron flux in distinct sites and directions. Because other iron-transport proteins remain active, labile iron gradients build up across the corresponding protein-deficient membranes. Here we report that a small-molecule natural product, hinokitiol, can harness such gradients to restore iron transport into, within, and/or out of cells. The same compound promotes gut iron absorption in DMT1-deficient rats and ferroportin-deficient mice, as well as hemoglobinization in DMT1- and mitoferrin-deficient zebrafish. These findings illuminate a general mechanistic framework for small molecule-mediated site- and direction-selective restoration of iron transport. They also suggest that small molecules that partially mimic the function of missing protein transporters of iron, and possibly other ions, may have potential in treating human diseases.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes