Iron control of erythroid microtubule cytoskeleton as a potential target in treatment of iron-restricted anemia

Adam N. Goldfarb, Katie C. Freeman, Ranjit K. Sahu, Kamaleldin E. Elagib, Maja Holy, Abhinav Arneja, Renata Polanowska-Grabowska, Alejandro A. Gru, Zollie White, Shadi Khalil, Michael J. Kerins, Aikseng Ooi, Norbert Leitinger, Chance John Luckey, Lorrie L. Delehanty

Research output: Contribution to journalArticlepeer-review

Abstract

Anemias of chronic disease and inflammation (ACDI) result from restricted iron delivery to erythroid progenitors. The current studies reveal an organellar response in erythroid iron restriction consisting of disassembly of the microtubule cytoskeleton and associated Golgi disruption. Isocitrate supplementation, known to abrogate the erythroid iron restriction response, induces reassembly of microtubules and Golgi in iron deprived progenitors. Ferritin, based on proteomic profiles, regulation by iron and isocitrate, and putative interaction with microtubules, is assessed as a candidate mediator. Knockdown of ferritin heavy chain (FTH1) in iron replete progenitors induces microtubule collapse and erythropoietic blockade; conversely, enforced ferritin expression rescues erythroid differentiation under conditions of iron restriction. Fumarate, a known ferritin inducer, synergizes with isocitrate in reversing molecular and cellular defects of iron restriction and in oral remediation of murine anemia. These findings identify a cytoskeletal component of erythroid iron restriction and demonstrate potential for its therapeutic targeting in ACDI.

Original languageEnglish (US)
Article number1645
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint

Dive into the research topics of 'Iron control of erythroid microtubule cytoskeleton as a potential target in treatment of iron-restricted anemia'. Together they form a unique fingerprint.

Cite this