Work

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

Year: 2026

Type: article

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.

Source: iScience

DOI: 10.1016/j.isci.2026.114738