Work

Modulation of intestinal sulfur assimilation metabolism regulates iron homeostasis

Year: 2018

Type: article

Abstract: 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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1715302115

Authors: Benjamin H. Hudson, Andrew T. Hale, Ryan P. Irving, Shenglan Li, John D. York

Institutions: Howard Hughes Medical Institute, Duke University, Vanderbilt University

Language: English

Topic: Iron Metabolism and Disorders

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDGs: Good health and well-being, Zero hunger

Open Access status: hybrid