Hong 2022 Cell Stem Cell

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 (2022) Mitochondrial dynamics maintain muscle stem cell regenerative competence throughout adult life by regulating metabolism and mitophagy. https://doi.org/10.1016/j.stem.2022.07.009

» Cell Stem Cell 29:1298-314.e10. PMID: 35998641 Open Access

Hong Xiaotong, Isern Joan, Campanario Silvia, Perdiguero Eusebio, Ramirez-Pardo Ignacio, Segales Jessica, Hernansanz-Agustin Pablo, Curtabbi Andrea, Deryagin Oleg, Pollan Agnela, Gonzalez-Reyes Jose A, Villalba Jose M, Sandri Marco, Serrano Antonio L, Enriquez Jose A, Munoz-Canoves Pura (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. • Keywords: Drp1, OXPHOS, Aging, Metabolism, Mitochondria, Mitochondrial dynamics, Mitophagy, Muscle regeneration, Muscle stem cells, Satellite cells • Bioblast editor: Plangger M • O2k-Network Lab: ES Madrid Enriquez JA

Labels: MiParea: Respiration, mt-Structure;fission;fusion  Pathology: Aging;senescence 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized cells 

Coupling state: LEAK, OXPHOS  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k 

2022-08