Open AccessThe mitochondrial unfolded protein response is activated upon hematopoietic stem cell exit from quiescence
Author(s) -
Mohrin Mary,
Widjaja Andrew,
Liu Yufei,
Luo Hanzhi,
Chen Danica
Publication year - 2018
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12756
Subject(s) - proteostasis , biology , stem cell , microbiology and biotechnology , unfolded protein response , haematopoiesis , hematopoietic stem cell , mitochondrion , endoplasmic reticulum
Summary The mitochondrial unfolded protein response ( UPR mt ), a cellular protective program that ensures proteostasis in the mitochondria, has recently emerged as a regulatory mechanism for adult stem cell maintenance that is conserved across tissues. Despite the emerging genetic evidence implicating the UPR mt in stem cell maintenance, the underlying molecular mechanism is unknown. While it has been speculated that the UPR mt is activated upon stem cell transition from quiescence to proliferation, the direct evidence is lacking. In this study, we devised three experimental approaches that enable us to monitor quiescent and proliferating hematopoietic stem cells ( HSC s) and provided the direct evidence that the UPR mt is activated upon HSC transition from quiescence to proliferation, and more broadly, mitochondrial integrity is actively monitored at the restriction point to ensure metabolic fitness before stem cells are committed to proliferation.