Cited by 213Muscle Physiology and DisordersMitochondrial Function and PathologyAdipose Tissue and Metabolism

Mitochondrial dynamics maintain muscle stem cell regenerative competence throughout adult life by regulating metabolism and mitophagy

Open access
Hong, Xiaotong, Isern, Joan, Campanario, Silvia, Perdiguero, Eusebio, Ramírez-Pardo, Ignacio, Segalés, Jessica, Hernansanz-Agustín, Pablo, Curtabbi, Andrea +8 more·2022·Cell stem cell

Abstract

Skeletal muscle regeneration depends on the correct expansion of resident quiescent stem cells (satellite cells), a process that becomes less efficient with aging. Here, we show that mitochondrial dynamics are essential for the successful regenerative capacity of satellite cells. The loss of mitochondrial fission in satellite cells-due to aging or genetic impairment-deregulates the mitochondrial electron transport chain (ETC), leading to inefficient oxidative phosphorylation (OXPHOS) metabolism and mitophagy and increased oxidative stress. This state results in muscle regenerative failure, which is caused by the reduced proliferation and functional loss of satellite cells. Regenerative functions can be restored in fission-impaired or aged satellite cells by the re-establishment of mitochondrial dynamics (by activating fission or preventing fusion), OXPHOS, or mitophagy. Thus, mitochondrial shape and physical networking controls stem cell regenerative functions by regulating metabolism and proteostasis. As mitochondrial fission occurs less frequently in the satellite cells in older humans, our findings have implications for regeneration therapies in sarcopenia.

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Registry

Crossref · 10.1016/j.stem.2022.07.009

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80 of 80 references verified0 citation errors · 0 not checkable

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  • During ageing, tissue regenerative functions decline, in part due to stem cell-intrinsic accumulation of damage, functional decay of niche cells and increased inflammation (inflammageing) through uncharacterized mechanisms.

    “During ageing, tissue regenerative functions decline, in part due to stem cell-intrinsic accumulation of damage (for example, DNA damage, loss of proteostasis and oxidative damage), functional decay of niche cells and increased inflammation (inflammageing)4–9 through uncharacterized mechanisms.”
  • Mitochondrial dynamics is essential for regulating muscle stem cell regeneration by regulating metabolism, protein balance, and mitophagy for regenerative therapies in sarcopenia.

    “This process is essential for regulating muscle stem cell regeneration by regulating metabolism, protein balance, and mitophagy for regenerative therapies in sarcopenia [56].”

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Authors
Hong, X., Isern, J., Campanario, S., Perdiguero, E., Ramírez-Pardo, I., Segalés, J., Hernansanz-Agustín, P., Curtabbi, A., Deryagin, O., Pollán, A., González-Reyes, J. A., Villalba, J. M., Sandri, M., Serrano, A. L., Enríquez, J. A., & Muñoz-Cánoves, P.
Affiliations
  • Spanish National Centre for Cardiovascular Research (ES)
  • Universitat Pompeu Fabra (ES)
  • University of Córdoba (ES)
  • University of Padua (IT)
Venue
Cell stem cell
Publisher
Elsevier BV
Published
2022-09
Volume
29
Issue
9
Pages
1298-1314.e10
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W4292646798
Cited by
213
References
81
Citations by year
2026: 53 · 2025: 68 · 2024: 51 · 2023: 36 · 2022: 5
FWCI
13.05
Type
journal article
Language
en
Update notices
erratum (2022-10-06)
Open access
Locations
  • Cell stem cell (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by-nc-nd)
  • Padua Research Archive (University of Padova) (submittedVersion)
Funders
  • Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES16/10/00282)
  • Milky Way Research Foundation
  • European Commission (H2020, 202033, 825825)
  • Associazione Italiana per la Ricerca sul Cancro
  • Centro Nacional de Investigaciones Cardiovasculares (MDM-2014-0370, SEV‐2015‐0505, HR17-00040, ERC-2016-AdG-741966, UPGRADE-H2020-825825)
  • Horizon 2020 Framework Programme (UPGRADE-H2020-825825, 825825)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
mitochondrial dynamics, satellite cells, muscle regeneration, aging, mitochondrial fission, mitochondrial fusion, mitophagy, oxidative phosphorylation, electron transport chain, oxidative stress, stem cell quiescence, sarcopenia, skeletal muscle stem cells
MeSH terms
Aged, Humans, Mitochondria, Muscles, Stem Cells, Muscle, Skeletal, Mitochondrial Dynamics, Mitophagy

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