Scinderin promotes fusion of electron transport chain dysfunctional muscle stem cells with myofibers.

Autor: Wang X; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Shelton SD; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Bordieanu B; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Present Address: Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425 USA., Frank AR; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Department of Internal Medicine, Division of Endocrinology, Program in Molecular Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA., Yi Y; Department of Comprehensive Dentistry, College of Dentistry, Texas A&M University, Dallas, TX 75246, USA.; Present address: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041 China., Venigalla SSK; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Gu Z; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Lenser NP; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Present address: Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Glogauer M; Faculty of Dentistry, University of Toronto, Toronto, ON, Canada., Chandel NS; Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.; Department of Biochemistry & Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Zhao H; Department of Comprehensive Dentistry, College of Dentistry, Texas A&M University, Dallas, TX 75246, USA.; Present address: The Chinese Institute for Brain Research, Beijing, China., Zhao Z; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., McFadden DG; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Department of Internal Medicine, Division of Endocrinology, Program in Molecular Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA., Mishra P; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Jazyk: angličtina
Zdroj: Nature aging [Nat Aging] 2022; Vol. 2 (2), pp. 155-169. Date of Electronic Publication: 2022 Jan 27.
DOI: 10.1038/s43587-021-00164-x
Abstrakt: Muscle stem cells (MuSCs) experience age-associated declines in number and function, accompanied by mitochondrial electron transport chain (ETC) dysfunction and increased reactive oxygen species (ROS). The source of these changes, and how MuSCs respond to mitochondrial dysfunction, is unknown. We report here that in response to mitochondrial ROS, murine MuSCs directly fuse with neighboring myofibers; this phenomenon removes ETC-dysfunctional MuSCs from the stem cell compartment. MuSC-myofiber fusion is dependent on the induction of Scinderin, which promotes formation of actin-dependent protrusions required for membrane fusion. During aging, we find that the declining MuSC population accumulates mutations in the mitochondrial genome, but selects against dysfunctional variants. In the absence of clearance by Scinderin, the decline in MuSC numbers during aging is repressed; however, ETC-dysfunctional MuSCs are retained and can regenerate dysfunctional myofibers. We propose a model in which ETC-dysfunctional MuSCs are removed from the stem cell compartment by fusing with differentiated tissue.
Databáze: MEDLINE