Mitochondrial Regulation in Stem Cells

Overview

Journal Trends Cell Biol

Specialty Cell Biology

Date 2023 Nov 2

PMID 37919163

Authors

Yifei Wang

Marine Barthez

Danica Chen

Affiliations

Soon will be listed here.

Abstract

Stem cells persist throughout the lifespan to repair and regenerate tissues due to their unique ability to self-renew and differentiate. Here we reflect on the recent discoveries in stem cells that highlight a mitochondrial metabolic checkpoint at the restriction point of the stem cell cycle. Mitochondrial activation supports stem cell proliferation and differentiation by providing energy supply and metabolites as signaling molecules. Concomitant mitochondrial stress can lead to loss of stem cell self-renewal and requires the surveillance of various mitochondrial quality control mechanisms. During aging, a mitochondrial protective program mediated by several sirtuins becomes dysregulated and can be targeted to reverse stem cell aging and tissue degeneration, giving hope for targeting the mitochondrial metabolic checkpoint for treating tissue degenerative diseases.

Citing Articles

Exploring Potential Impact of Graphene Oxide and Graphene Oxide-Polyethylenimine on Biological Behavior of Human Amniotic Fluid-Derived Stem Cells.

Di Credico A, Gaggi G, Bibbo S, Pilato S, Moffa S, Di Giacomo S Int J Mol Sci. 2025; 25(24.

PMID: 39769359 PMC: 11678234. DOI: 10.3390/ijms252413598.

An NAD-dependent metabolic checkpoint regulates hematopoietic stem cell activation and aging.

Song Z, Park S, Mu W, Feng Y, Wang C, Wang Y Nat Aging. 2024; 4(10):1384-1393.

PMID: 39044033 PMC: 11565225. DOI: 10.1038/s43587-024-00670-8.

Sirtuins Affect Cancer Stem Cells via Epigenetic Regulation of Autophagy.

Sipos F, Muzes G Biomedicines. 2024; 12(2).

PMID: 38397988 PMC: 10886574. DOI: 10.3390/biomedicines12020386.

References

Ohkubo R, Mu W, Wang C, Song Z, Barthez M, Wang Y . The hepatic integrated stress response suppresses the somatotroph axis to control liver damage in nonalcoholic fatty liver disease. Cell Rep. 2022; 41(11):111803. PMC: 9825120. DOI: 10.1016/j.celrep.2022.111803. View

Golan K, Kumari A, Kollet O, Khatib-Massalha E, Subramaniam M, Ferreira Z . Daily Onset of Light and Darkness Differentially Controls Hematopoietic Stem Cell Differentiation and Maintenance. Cell Stem Cell. 2018; 23(4):572-585.e7. DOI: 10.1016/j.stem.2018.08.002. View

Berger E, Rath E, Yuan D, Waldschmitt N, Khaloian S, Allgauer M . Mitochondrial function controls intestinal epithelial stemness and proliferation. Nat Commun. 2016; 7:13171. PMC: 5080445. DOI: 10.1038/ncomms13171. View

Ludikhuize M, Meerlo M, Gallego M, Xanthakis D, Burgaya Julia M, Nguyen N . Mitochondria Define Intestinal Stem Cell Differentiation Downstream of a FOXO/Notch Axis. Cell Metab. 2020; 32(5):889-900.e7. DOI: 10.1016/j.cmet.2020.10.005. View

Senos Demarco R, Uyemura B, DAlterio C, Jones D . Mitochondrial fusion regulates lipid homeostasis and stem cell maintenance in the Drosophila testis. Nat Cell Biol. 2019; 21(6):710-720. DOI: 10.1038/s41556-019-0332-3. View

Ho T, Warr M, Adelman E, Lansinger O, Flach J, Verovskaya E . Autophagy maintains the metabolism and function of young and old stem cells. Nature. 2017; 543(7644):205-210. PMC: 5344718. DOI: 10.1038/nature21388. View

Zhou W, Zhao T, Du J, Ji G, Li X, Ji S . TIGAR promotes neural stem cell differentiation through acetyl-CoA-mediated histone acetylation. Cell Death Dis. 2019; 10(3):198. PMC: 6393469. DOI: 10.1038/s41419-019-1434-3. View

Mohrin M, Shin J, Liu Y, Brown K, Luo H, Xi Y . Stem cell aging. A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging. Science. 2015; 347(6228):1374-7. PMC: 4447312. DOI: 10.1126/science.aaa2361. View

Dong X, Zhang Q, Yu X, Wang D, Ma J, Ma J . Metabolic lactate production coordinates vasculature development and progenitor behavior in the developing mouse neocortex. Nat Neurosci. 2022; 25(7):865-875. DOI: 10.1038/s41593-022-01093-7. View

10.

Dong S, Wang Q, Kao Y, Diaz A, Tasset I, Kaushik S . Chaperone-mediated autophagy sustains haematopoietic stem-cell function. Nature. 2021; 591(7848):117-123. PMC: 8428053. DOI: 10.1038/s41586-020-03129-z. View

11.

Friedman J, Nunnari J . Mitochondrial form and function. Nature. 2014; 505(7483):335-43. PMC: 4075653. DOI: 10.1038/nature12985. View

12.

Mortensen M, Soilleux E, Djordjevic G, Tripp R, Lutteropp M, Sadighi-Akha E . The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J Exp Med. 2011; 208(3):455-67. PMC: 3058574. DOI: 10.1084/jem.20101145. View

13.

Mohrin M, Widjaja A, Liu Y, Luo H, Chen D . The mitochondrial unfolded protein response is activated upon hematopoietic stem cell exit from quiescence. Aging Cell. 2018; 17(3):e12756. PMC: 5946069. DOI: 10.1111/acel.12756. View

14.

Jin G, Xu C, Zhang X, Long J, Rezaeian A, Liu C . Atad3a suppresses Pink1-dependent mitophagy to maintain homeostasis of hematopoietic progenitor cells. Nat Immunol. 2017; 19(1):29-40. PMC: 5905408. DOI: 10.1038/s41590-017-0002-1. View

15.

Murakami K, Kurotaki D, Kawase W, Soma S, Fukuchi Y, Kunimoto H . OGT Regulates Hematopoietic Stem Cell Maintenance via PINK1-Dependent Mitophagy. Cell Rep. 2021; 34(1):108579. DOI: 10.1016/j.celrep.2020.108579. View

16.

Sheng X, Liu C, Yan G, Li G, Liu J, Yang Y . The mitochondrial protease LONP1 maintains oocyte development and survival by suppressing nuclear translocation of AIFM1 in mammals. EBioMedicine. 2022; 75:103790. PMC: 8733232. DOI: 10.1016/j.ebiom.2021.103790. View

17.

Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P . NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016; 352(6292):1436-43. DOI: 10.1126/science.aaf2693. View

18.

Takubo K, Goda N, Yamada W, Iriuchishima H, Ikeda E, Kubota Y . Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. Cell Stem Cell. 2010; 7(3):391-402. DOI: 10.1016/j.stem.2010.06.020. View

19.

Rossmann M, Hoi K, Chan V, Abraham B, Yang S, Mullahoo J . Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis. Science. 2021; 372(6543):716-721. PMC: 8177078. DOI: 10.1126/science.aaz2740. View

20.

Wu M, Chen Y, Kim M, Chang C, Gampala S, Zhang Y . Epithelial-Mesenchymal Transition Directs Stem Cell Polarity via Regulation of Mitofusin. Cell Metab. 2018; 29(4):993-1002.e6. DOI: 10.1016/j.cmet.2018.11.004. View