Stress-induced reversible cell-cycle arrest requires PRC2/PRC1-mediated control of mitophagy in Drosophila germline stem cells and human iPSCs

Tommy H. Taslim; Abdiasis M. Hussein; Riya Keshri; Julien R. Ishibashi; Tung C. Chan; Bich N. Nguyen; Shuozhi Liu; Daniel Brewer; Stuart Harper; Scott Lyons; Ben Garver; Jimmy Dang; Nanditaa Balachandar; Samriddhi Jhajharia; Debra del Castillo; Julie Mathieu; Hannele Ruohola-Baker

Stem Cell Reports (Jan 2023)

Stress-induced reversible cell-cycle arrest requires PRC2/PRC1-mediated control of mitophagy in Drosophila germline stem cells and human iPSCs

Tommy H. Taslim,
Abdiasis M. Hussein,
Riya Keshri,
Julien R. Ishibashi,
Tung C. Chan,
Bich N. Nguyen,
Shuozhi Liu,
Daniel Brewer,
Stuart Harper,
Scott Lyons,
Ben Garver,
Jimmy Dang,
Nanditaa Balachandar,
Samriddhi Jhajharia,
Debra del Castillo,
Julie Mathieu,
Hannele Ruohola-Baker

Affiliations

Tommy H. Taslim: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA
Abdiasis M. Hussein: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA
Riya Keshri: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA
Julien R. Ishibashi: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA
Tung C. Chan: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA
Bich N. Nguyen: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA
Shuozhi Liu: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA
Daniel Brewer: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA
Stuart Harper: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA
Scott Lyons: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA
Ben Garver: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA
Jimmy Dang: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA
Nanditaa Balachandar: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA; Department of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, India
Samriddhi Jhajharia: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA; Department of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, India
Debra del Castillo: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA
Julie Mathieu: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA; Department of Comparative Medicine, University of Washington, Seattle, WA, USA
Hannele Ruohola-Baker: Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, WA, USA; Corresponding author

Journal volume & issue: Vol. 18, no. 1
pp. 269 – 288

Abstract

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Summary: Following acute genotoxic stress, both normal and tumorous stem cells can undergo cell-cycle arrest to avoid apoptosis and later re-enter the cell cycle to regenerate daughter cells. However, the mechanism of protective, reversible proliferative arrest, “quiescence,” remains unresolved. Here, we show that mitophagy is a prerequisite for reversible quiescence in both irradiated Drosophila germline stem cells (GSCs) and human induced pluripotent stem cells (hiPSCs). In GSCs, mitofission (Drp1) or mitophagy (Pink1/Parkin) genes are essential to enter quiescence, whereas mitochondrial biogenesis (PGC1α) or fusion (Mfn2) genes are crucial for exiting quiescence. Furthermore, mitophagy-dependent quiescence lies downstream of mTOR- and PRC2-mediated repression and relies on the mitochondrial pool of cyclin E. Mitophagy-dependent reduction of cyclin E in GSCs and in hiPSCs during mTOR inhibition prevents the usual G1/S transition, pushing the cells toward reversible quiescence (G0). This alternative method of G1/S control may present new opportunities for therapeutic purposes.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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