Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice


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Leduc-Gaudet, J. P., Picard, M., Pelletier, F. S. J., Sgarioto, N., Auger, M. J., Vallée, J., Robitaille, R., St-Pierre, D. H. et Gouspillou, G. (2015). Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice. Oncotarget, 6 (20). pp. 17923-17937. ISSN 1949-2553 DOI 10.18632/oncotarget.4235

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Skeletal muscle aging is associated with a progressive decline in muscle mass and strength, a process termed sarcopenia. Evidence suggests that accumulation of mitochondrial dysfunction plays a causal role in sarcopenia, which could be triggered by impaired mitophagy. Mitochondrial function, mitophagy and mitochondrial morphology are interconnected aspects of mitochondrial biology, and may coordinately be altered with aging. However, mitochondrial morphology has remained challenging to characterize in muscle, and whether sarcopenia is associated with abnormal mitochondrial morphology remains unknown. Therefore, we assessed the morphology of SubSarcolemmal (SS) and InterMyoFibrillar (IMF) mitochondria in skeletal muscle of young (8-12wk-old) and old (88-96wk-old) mice using a quantitative 2-dimensional transmission electron microscopy approach. We show that sarcopenia is associated with larger and less circular SS mitochondria. Likewise, aged IMF mitochondria were longer and more branched, suggesting increased fusion and/or decreased fission. Accordingly, although no difference in the content of proteins regulating mitochondrial dynamics (Mfn1, Mfn2, Opa1 and Drp1) was observed, a mitochondrial fusion index (Mfn2-to-Drp1 ratio) was significantly increased in aged muscles. Our results reveal that sarcopenia is associated with complex changes in mitochondrial morphology that could interfere with mitochondrial function and mitophagy, and thus contribute to aging-related accumulation of mitochondrial dysfunction and sarcopenia.

Type de document: Article
Mots-clés libres: Atrophy Mitochondria Mitochondrial dynamics Muscle aging Sarcopenia Drp1 protein Mitofusin 1 Mitofusin 2 Muscle protein Opa1 protein Unclassified drug Dnm1l protein, mouse Dynamin Guanosine triphosphatase Mfn1 protein, mouse Mfn2 protein, mouse Opa1 protein (GTPase), mouse Adult Aged Aging Animal cell Animal experiment Animal model Animal tissue Article Cell structure Disease association Disorders of mitochondrial functions Gastrocnemius muscle Male Mitochondrial fusion index Mitophagy Mouse Muscle fibril Muscle mitochondrion Musculoskeletal system parameters Nonhuman Protein content Quantitative analysis Sarcolemma Transmission electron microscopy Age Animal Comparative study Disease model Metabolism Mitochondrial volume Organelle shape Pathology Skeletal muscle Ultrastructure Age Factors Animals Disease Models, Animal Dynamins GTP Phosphohydrolases Mice Microscopy, Electron, Transmission Mitochondria, Muscle Mitochondrial Size Muscle, Skeletal
Date de dépôt: 10 juill. 2023 18:18
Dernière modification: 10 juill. 2023 18:18
Version du document déposé: Version officielle de l'éditeur

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