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 and Lorrie L. Delehanty
Additional contact information
Adam N. Goldfarb: University of Virginia School of Medicine
Katie C. Freeman: University of Virginia School of Medicine
Ranjit K. Sahu: University of Virginia School of Medicine
Kamaleldin E. Elagib: University of Virginia School of Medicine
Maja Holy: University of Virginia School of Medicine
Abhinav Arneja: University of Virginia School of Medicine
Renata Polanowska-Grabowska: University of Virginia School of Medicine
Alejandro A. Gru: University of Virginia School of Medicine
Zollie White: University of Virginia School of Medicine
Shadi Khalil: University of California, San Diego School of Medicine
Michael J. Kerins: University of Arizona
Aikseng Ooi: University of Arizona
Norbert Leitinger: University of Virginia School of Medicine
Chance John Luckey: University of Virginia School of Medicine
Lorrie L. Delehanty: University of Virginia School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-21938-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21938-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-21938-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().