The mitochondrial protein OPA1 regulates the quiescent state of adult muscle stem cells
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved..
Quiescence regulation is essential for adult stem cell maintenance and sustained regeneration. Our studies uncovered that physiological changes in mitochondrial shape regulate the quiescent state of adult muscle stem cells (MuSCs). We show that MuSC mitochondria rapidly fragment upon an activation stimulus, via systemic HGF/mTOR, to drive the exit from deep quiescence. Deletion of the mitochondrial fusion protein OPA1 and mitochondrial fragmentation transitions MuSCs into G-alert quiescence, causing premature activation and depletion upon a stimulus. OPA1 loss activates a glutathione (GSH)-redox signaling pathway promoting cell-cycle progression, myogenic gene expression, and commitment. MuSCs with chronic OPA1 loss, leading to mitochondrial dysfunction, continue to reside in G-alert but acquire severe cell-cycle defects. Additionally, we provide evidence that OPA1 decline and impaired mitochondrial dynamics contribute to age-related MuSC dysfunction. These findings reveal a fundamental role for OPA1 and mitochondrial dynamics in establishing the quiescent state and activation potential of adult stem cells.
| Errataetall: |
CommentIn: Cell Stem Cell. 2022 Sep 1;29(9):1287-1289. - PMID 36055187 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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| Enthalten in: |
Cell stem cell - 29(2022), 9 vom: 01. Sept., Seite 1315-1332.e9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Baker, Nicole [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.09.2022 Date Revised 10.06.2023 published: Print-Electronic CommentIn: Cell Stem Cell. 2022 Sep 1;29(9):1287-1289. - PMID 36055187 Citation Status MEDLINE |
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| doi: |
10.1016/j.stem.2022.07.010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Quiescence regulation is essential for adult stem cell maintenance and sustained regeneration. Our studies uncovered that physiological changes in mitochondrial shape regulate the quiescent state of adult muscle stem cells (MuSCs). We show that MuSC mitochondria rapidly fragment upon an activation stimulus, via systemic HGF/mTOR, to drive the exit from deep quiescence. Deletion of the mitochondrial fusion protein OPA1 and mitochondrial fragmentation transitions MuSCs into G-alert quiescence, causing premature activation and depletion upon a stimulus. OPA1 loss activates a glutathione (GSH)-redox signaling pathway promoting cell-cycle progression, myogenic gene expression, and commitment. MuSCs with chronic OPA1 loss, leading to mitochondrial dysfunction, continue to reside in G-alert but acquire severe cell-cycle defects. Additionally, we provide evidence that OPA1 decline and impaired mitochondrial dynamics contribute to age-related MuSC dysfunction. These findings reveal a fundamental role for OPA1 and mitochondrial dynamics in establishing the quiescent state and activation potential of adult stem cells | ||
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| 700 | 1 | |a Wade, Steven |e verfasserin |4 aut | |
| 700 | 1 | |a Triolo, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Girgis, John |e verfasserin |4 aut | |
| 700 | 1 | |a Chwastek, Damian |e verfasserin |4 aut | |
| 700 | 1 | |a Larrigan, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Feige, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Fujita, Ryo |e verfasserin |4 aut | |
| 700 | 1 | |a Crist, Colin |e verfasserin |4 aut | |
| 700 | 1 | |a Rudnicki, Michael A |e verfasserin |4 aut | |
| 700 | 1 | |a Burelle, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Khacho, Mireille |e verfasserin |4 aut | |
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