The mitochondrial unfolded protein response is activated upon hematopoietic stem cell exit from quiescence

Mary Mohrin; Andrew Widjaja; Yufei Liu; Hanzhi Luo; Danica Chen

doi:10.1111/acel.12756

The mitochondrial unfolded protein response is activated upon hematopoietic stem cell exit from quiescence

Mary Mohrin, Andrew Widjaja, Yufei Liu, Hanzhi Luo, Danica Chen

Research output: Contribution to journal › Article › peer-review

64 Scopus citations

Abstract

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 (HSCs) 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.

Original language	English
Article number	e12756
Journal	Aging Cell
Volume	17
Issue number	3
DOIs	https://doi.org/10.1111/acel.12756
State	Published - Jun 2018

Bibliographical note

Publisher Copyright:
© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Funding

We thank H. Nolla, A. Valeros, and K. Heydari for cell sorting. This research was supported by NIH R01 AG040990 (D.C.), R01DK101885 (D.C.), National Institute of Food and Agriculture (D.C.), PackerWentz Endowment (D.C.), Chau Hoi Shuen Foundation (Chen), Siebel Stem Cell Institute (M.M., D.C.), NIH T32AG000266 (M.M.), NIH T32GM098218 (A.W.), and Glenn/AFAR Scholarship (H.L.).

Funders	Funder number
Chau Hoi Shuen Foundation	T32GM098218, T32AG000266
PackerWentz Endowment
National Institutes of Health (NIH)	R01DK101885
National Institutes of Health (NIH)
National Institute on Aging	R01AG040990
National Institute on Aging
US Department of Agriculture National Institute of Food and Agriculture, Agriculture and Food Research Initiative

Keywords

aging
hematopoietic stem cells
mitochondria
mitochondrial unfolded protein response
SIRT7
stem cell quiescence
stem cells

ASJC Scopus subject areas

Aging
Cell Biology

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10.1111/acel.12756

Cite this

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abstract = " 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 (HSCs) 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.",

keywords = "aging, hematopoietic stem cells, mitochondria, mitochondrial unfolded protein response, SIRT7, stem cell quiescence, stem cells",

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T1 - The mitochondrial unfolded protein response is activated upon hematopoietic stem cell exit from quiescence

AU - Mohrin, Mary

AU - Widjaja, Andrew

AU - Liu, Yufei

AU - Luo, Hanzhi

AU - Chen, Danica

PY - 2018/6

Y1 - 2018/6

N2 - 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 (HSCs) 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.

AB - 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 (HSCs) 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.

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KW - mitochondria

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KW - SIRT7

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KW - stem cells

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The mitochondrial unfolded protein response is activated upon hematopoietic stem cell exit from quiescence

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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