Regulation of Intracellular Iron Metabolism

Klausner, R D.

Abstract

The molecular basis of intracellular iron metabolism rests with the regulation of expression and assembly of ferritin. In order to understand the detailed mechanisms of this regulation we have cloned the entire functional gene for the heavy (H) chain of human ferritin. This gene has been fully characterized and has been introduced into mouse cells in order to dissect the genetic elements responsible for its regulated expression. In addition cross reacting sequences located near the HLA locus of chromosome 6 have been identified and are currently being cloned. This may provide a link to the genetic basis of hereditary hemochromatosis.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
• Type: Intramural Research (Z01)
• Project #: 1Z01HD001602-02
• Application #: 3965853
• Support Year: 2
• Fiscal Year: 1986

Institution

• Name: U.S. National Inst/Child Hlth/Human Dev
• Country: United States

Publications

Rouault, Tracey A; Tong, Wing-Hang (2009) Tangled up in red: intertwining of the heme and iron-sulfur cluster biogenesis pathways. Cell Metab 10:80-1

Tong, Wing-Hang; Rouault, Tracey A (2007) Metabolic regulation of citrate and iron by aconitases: role of iron-sulfur cluster biogenesis. Biometals 20:549-64

Crooks, Daniel R; Ghosh, Manik C; Braun-Sommargren, Michelle et al. (2007) Manganese targets m-aconitase and activates iron regulatory protein 2 in AF5 GABAergic cells. J Neurosci Res 85:1797-809

Missirlis, Fanis; Kosmidis, Stylianos; Brody, Tom et al. (2007) Homeostatic mechanisms for iron storage revealed by genetic manipulations and live imaging of Drosophila ferritin. Genetics 177:89-100

Zhang, Deliang; Meyron-Holtz, Esther; Rouault, Tracey A (2007) Renal iron metabolism: transferrin iron delivery and the role of iron regulatory proteins. J Am Soc Nephrol 18:401-6

Rouault, Tracey A; Cooperman, Sharon (2006) Brain iron metabolism. Semin Pediatr Neurol 13:142-8

Rouault, Tracey A (2006) Biochemistry. If the RNA fits, use it. Science 314:1886-7

Smith, Sophia R; Ghosh, Manik C; Ollivierre-Wilson, Hayden et al. (2006) Complete loss of iron regulatory proteins 1 and 2 prevents viability of murine zygotes beyond the blastocyst stage of embryonic development. Blood Cells Mol Dis 36:283-7

Lind, Maria I; Missirlis, Fanis; Melefors, Ojar et al. (2006) Of two cytosolic aconitases expressed in Drosophila, only one functions as an iron-regulatory protein. J Biol Chem 281:18707-14

Missirlis, Fanis; Holmberg, Sara; Georgieva, Teodora et al. (2006) Characterization of mitochondrial ferritin in Drosophila. Proc Natl Acad Sci U S A 103:5893-8