Modulation of intestinal sulfur assimilation metabolism regulates iron homeostasis.
Journal Article (Journal Article)
Sulfur assimilation is an evolutionarily conserved pathway that plays an essential role in cellular and metabolic processes, including sulfation, amino acid biosynthesis, and organismal development. We report that loss of a key enzymatic component of the pathway, bisphosphate 3'-nucleotidase (Bpnt1), in mice, both whole animal and intestine-specific, leads to iron-deficiency anemia. Analysis of mutant enterocytes demonstrates that modulation of their substrate 3'-phosphoadenosine 5'-phosphate (PAP) influences levels of key iron homeostasis factors involved in dietary iron reduction, import and transport, that in part mimic those reported for the loss of hypoxic-induced transcription factor, HIF-2α. Our studies define a genetic basis for iron-deficiency anemia, a molecular approach for rescuing loss of nucleotidase function, and an unanticipated link between nucleotide hydrolysis in the sulfur assimilation pathway and iron homeostasis.
Full Text
Duke Authors
Cited Authors
- Hudson, BH; Hale, AT; Irving, RP; Li, S; York, JD
Published Date
- March 20, 2018
Published In
Volume / Issue
- 115 / 12
Start / End Page
- 3000 - 3005
PubMed ID
- 29507250
Pubmed Central ID
- PMC5866552
Electronic International Standard Serial Number (EISSN)
- 1091-6490
Digital Object Identifier (DOI)
- 10.1073/pnas.1715302115
Language
- eng
Conference Location
- United States