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Role of mytofusin 1 in adaptations induced by physical exercise in skeletal muscle

Grant number: 21/05746-7
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2021
Effective date (End): July 31, 2023
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Julio Cesar Batista Ferreira
Grantee:Jones Raul Laureano Meneses
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Changes in mitochondrial dynamics (fusion / fission) alter the morphology and bioenergetics of mitochondria. Physical exercise in turn is a positive regulator of skeletal muscle metabolic functions. Recently, our group demonstrated that the reestablishment of the mitochondrial fusion-fission balance through physical exercise is sufficient to recover the mitochondrial bioenergetic metabolism and improve the prognosis of heart failure in rodents. This process occurs via the reestablishment of the catalytic activity of mitofusin 1 (Mfn1, GTPase important in mitochondrial fusion) in cardiac tissue. Considering that skeletal muscles present a high metabolic demand and a large amount of mitochondria, we decided to investigate the role of mitochondrial plasticity in skeletal muscle. We hypothesized that the absence of Mfn1 protein in skeletal muscle will result in the sustained accumulation of fragmented and dysfunctional mitochondria, and that the absence of Mfn1 will block the positive effects of physical training on mitochondrial morphological and bioenergetic changes in skeletal muscle. For this, transgenic mice with muscle-specific deletion of mitofusin 1 (Mfn1flox / ACTA1Cre) will be submitted to a physical training protocol on a treadmill. 48 hours after the last exercise session, the morphology and contractile function of the skeletal musculature, as well as the mitochondrial bioenergetics and the protein content related to the mitochondrial dynamics will be analyzed. It should be noted that the animal colony has already been established in our laboratory. In addition, for this study we will have the infrastructure and collaboration of Prof. Dr. Julio Cesar Batista Ferreira. (AU)

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