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Iron Restriction Alleviates β-Thalassemia By Stimulating ULK1-Mediated Autophagy of Free α-Globin

Authors :
Fernandez, Alfonso G.
Christakopoulos, Georgios E.
Michael, Dudley E.
Sweileh, Razan B. A.
Telange, Rahul
Sheppard, Heather
Yao, Yu
Zhang, Jingjing
Manolova, Vania
Nemeth, Elizabeta
Ganz, Tomas
Weiss, Mitchell J.
Source :
Blood; November 2023, Vol. 142 Issue: 1, Number 1 Supplement 1 p558-558, 1p
Publication Year :
2023

Abstract

In β-thalassemia, mutations in the HBBgene cause reduced β-globin synthesis with accumulation of toxic free α-globin, leading to ineffective erythropoiesis and hemolysis. We showed previously that β-thalassemic erythroblasts can eliminate free α-globin by ULK1-mediated autophagy and that this process is stimulated by rapamycin inhibition of mTORC1, which phosphorylates ULK1 to inhibit its activity. Several studies have shown that iron restriction can reduce the accumulation of free α-globin precipitates to alleviate the pathophysiology of β-thalassemia. Considering that iron stimulates mTORC1 activity in numerous cell types including erythroblasts, we tested the hypothesis that iron restriction alleviates β-thalassemia by inhibiting mTORC1, thereby stimulating ULK1-mediated autophagy of free α-globin.

Details

Language :
English
ISSN :
00064971 and 15280020
Volume :
142
Issue :
1, Number 1 Supplement 1
Database :
Supplemental Index
Journal :
Blood
Publication Type :
Periodical
Accession number :
ejs64699593
Full Text :
https://doi.org/10.1182/blood-2023-185008