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

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 mitocho...

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Bibliographic Details
Authors: Hong, Xiaotong, Isern, Joan, Campanario, Silvia, Perdiguero, Eusebio, Ramírez-Pardo, Ignacio, Segalés, Jessica, Hernansanz-Agustín, Pablo, Curtabbi, Andrea, Deryagin, Oleg, Pollán, Angela, González-Reyes, José A, Villalba, José M, Sandri, Marco, Serrano, Antonio L, Enriquez, Jose Antonio, Muñoz-Cánoves, Pura
Format: article
Publication Date:2022
Country:España
Institution:Instituto de Salud Carlos III (ISCIII)
Repository:Repisalud
Language:English
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/15674
Online Access:http://hdl.handle.net/20.500.12105/15674
Access Level:Open access
Keyword:Mitochondrial Dynamics
Mitophagy
Aged
Humans
Mitochondria
Muscle, Skeletal
Muscles
Stem Cells
Description
Summary: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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