Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice

// Jean-Philippe Leduc-Gaudet 1,2,3 , Martin Picard 4 , Félix St-Jean Pelletier 1 , Nicolas Sgarioto 1 , Marie-Joëlle Auger 1 , Joanne Vallée 5 , Richard Robitaille 5,6 , David H. St-Pierre 1,2,3 and Gilles Gouspillou 1,2,7 1 Département des Sciences de l’Activité Physique, Faculté des Sciences, UQAM, Montréal, Canada 2 Groupe de Recherche en Activité Physique Adaptée, Montréal, Canada 3 Centre de Recherche du CHU Sainte-Justine, Montréal, Canada 4 The Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA, USA 5 Département de Neurosciences, Université de Montréal, Montréal, Canada 6 Groupe de Recherche sur le Système Nerveux Central, Montréal, Canada 7 Centre de Recherche de l’Institut Universitaire de Gériatrie de Montréal, Montréal, Canada Correspondence to: Gilles Gouspillou, email: // Keywords : mitochondria, muscle aging, atrophy, sarcopenia, mitochondrial dynamics Received : March 16, 2015 Accepted : May 12, 2015 Published : May 22, 2015 Abstract 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(definition) 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.