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

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• dc.contributor.author Hong, Xiaotong
• dc.contributor.author Isern, Joan
• dc.contributor.author Campanario, Silvia
• dc.contributor.author Perdiguero, Eusebio, 1968-
• dc.contributor.author Ramírez Pardo, Ignacio
• dc.contributor.author Segalés Dalmau, Jessica
• dc.contributor.author Hernansanz-Agustín, Pablo
• dc.contributor.author Curtabbi, Andrea
• dc.contributor.author Deryagin, Oleg
• dc.contributor.author Pollán, Angela
• dc.contributor.author González-Reyes, José A.
• dc.contributor.author Villalba, José M.
• dc.contributor.author Sandri, Marco
• dc.contributor.author Serrano Sánchez, Antonio L.
• dc.contributor.author Enríquez, José Antonio
• dc.contributor.author Muñoz Cánoves, Pura, 1962-
• dc.date.accessioned 2022-11-14T07:13:16Z
• dc.date.available 2022-11-14T07:13:16Z
• dc.date.issued 2022
• dc.description.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.
• dc.description.sponsorship Work in the PMC laboratory was supported by Spanish Ministerio de Ciencia e Innovación ( RTI2018-096068 to P.M.-C. and E.P), ERC - 2016-AdG-741966 , LaCaixa - HEALTH-HR17-00040 , MDA , UPGRADE-H2020-825825 , AFM-Telethon , DPP-Spain , Fundació La Marató TV3-80/19-202021 to P.M.-C; Fundació La Marató TV3-137/38-202033 to A.L.S.; partly supported by Milky Way Research Foundation (MWRF) to P.M.-C; Severo Ochoa Program for Centers of Excellence to CNIC ( SEV-2015-0505 ) and Maria de Maeztu Program for Units of Excellence to UPF ( MDM-2014-0370 ). Work in the JAE laboratory was supported by Ministerio de Ciencia e Innovacion ( RTI2018-099357-B-I00 , RED2018-102576-T ), Human Frontier Science Program HFSP ( RGP0016/2018 ), Centro de Investigación Biomédica en Red en Fragilidad y Envejecimento Saludable ( CIBERFES16/10/00282 ), and Leduq Foundation award ( REDOX-17CVD04 ). Work in JMV laboratory was supported by the Spanish Ministerio de Ciencia e Innovación ( RTI2018-100695-B-I00 ), Spanish Junta de Andalucía ( P18-RT-4264 , 1263735-R and BIO-276 ), the FEDER Funding Program from the European Union , and Universidad de Córdoba . The authors are indebted to the personnel from the Servicio Centralizado de Apoyo a la Investigación (SCAI; University of Córdoba) for technical support with the transmission electron microscope. Work in MS laboratory was funded by the Italian Assoc. for Cancer Research ( AIRC IG-D17388 and ID23257 ) and ASI (MARS-PRE, project DC-VUM-2017-006). X.H., S.C., I.R.-P, and A.C were supported by Severo Ochoa PFI , PI , FPI , and H2020 Marie Skłodowska-Curie Actions predoctoral fellowships, respectively. P.H.-A was supported by Juan de la Cierva-Incorporación fellowship.
• dc.format.mimetype application/pdf
• dc.identifier.citation Hong X, Isern J, Campanario S, Perdiguero E, Ramírez-Pardo I, Segalés J, Hernansanz-Agustín P, Curtabbi A, Deryagin O, Pollán A, González-Reyes JA, Villalba JM, Sandri M, Serrano AL, Enríquez JA, Muñoz-Cánoves P. Mitochondrial dynamics maintain muscle stem cell regenerative competence throughout adult life by regulating metabolism and mitophagy. Cell Stem Cell. 2022 Sep 1;29(9):1298-1314.e10. DOI: 10.1016/j.stem.2022.07.009
• dc.identifier.doi http://dx.doi.org/10.1016/j.stem.2022.07.009
• dc.identifier.issn 1934-5909
• dc.identifier.uri http://hdl.handle.net/10230/54828
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Cell Stem Cell. 2022 Sep 1;29(9):1298-1314.e10
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/741966
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-096068
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/825825
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-099357-B-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RED2018-102576-T
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-100695-B-I00
• dc.rights © 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Drp1
• dc.subject.keyword OXPHOS
• dc.subject.keyword Aging
• dc.subject.keyword Metabolism
• dc.subject.keyword Mitochondria
• dc.subject.keyword Mitochondrial dynamics
• dc.subject.keyword Mitophagy
• dc.subject.keyword Muscle regeneration
• dc.subject.keyword Muscle stem cells
• dc.subject.keyword Satellite cells
• dc.title Mitochondrial dynamics maintain muscle stem cell regenerative competence throughout adult life by regulating metabolism and mitophagy
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion