Heritable ER stress impairs mitochondrial metabolism and maintenance of hematopoietic stem cells after low-dose irradiation

iScience 2026 Open access

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Authors: Stephanie G. Moreno, Federica Ferri, Daniel Lewandowski, Vilma Barroca, Saiyiramii Devanand, Nathalie Déchamps, Paul‐Henri Roméo, Gault Nathalie
DOI: 10.1016/j.isci.2026.114738
Cited by: 1
References: 70

Abstract

overload. These mitochondrial defects arise from immediate and sustained endoplasmic reticulum (ER) stress, induced by proliferative 20 mGy-HSC through the activation of the eIF2α-ATF4 branch of the unfolded protein response (UPR). The ER stress is heritable and leads, in long-term quiescent 20 mGy-HSC, to the activation of the IRE1α-Xbp1 branch of UPR, which fails to restore ER homeostasis, resulting in a decreased long-term HSC pool. Finally, we show that this heritable ER stress leads to global DNA hypomethylation, partially reversed by the early inhibition of ER stress. Our studies illuminate how adaptive ER stress responses can lead to mitochondrial defects and HSC dysfunctions.

Fields of Study & Subjects

Endoplasmic Reticulum Stress and Disease Effects of Radiation Exposure DNA Repair Mechanisms

Publication details

Journal / source
iScience
Publisher
Elsevier BV
Volume
29
Issue
2
Pages
114738–114738
Publication date
20 January 2026
Language
EN