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Molecular mechanisms of aerobic exercise-induced mitophagy in skeletal muscle

Grant number: 14/26797-5
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): March 02, 2015
Effective date (End): March 01, 2016
Field of knowledge:Health Sciences - Physical Education
Principal Investigator:Patricia Chakur Brum
Grantee:Paulo Roberto Jannig
Supervisor: Jorge Lira Ruas
Host Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Karolinska Institutet, Sweden  
Associated to the scholarship:13/21065-3 - Aerobic exercise-induced mitochondrial adaptation: role of muscle mitophagy, BP.DR


Exercise capacity is the most powerful predictor of all-cause mortality even when compared to other established risk factors like obesity, diabetes, hypertension, and smoking. Thus, physical inactivity is one of the leading modifiable risk factors to be fought against the worldwide burden of non-communicable diseases. The increase in oxidative capacity induced by aerobic exercise is considered the major factor for its health benefits. These beneficial effects arise from acute and chronic adaptations in a variety of organic systems, which promotes resistance against homeostasis breakdown by metabolic perturbations. Indeed, aerobic exercise-trained muscles show several structural and metabolic adaptations that culminate in a higher oxidative phenotype. Alterations in mitochondrial function and structure play a central role in improving oxidative metabolism, which requires the coordinated action of mitochondrial biogenesis, fission, fusion and autophagy. The role of mitochondrial biogenesis has already been extensively investigated, showing that PGC-1±1 is a master regulator of this process. Despite some studies have recently shown that mitochondrial degradation by autophagy (mitophagy) is an important step to mitochondrial quality control following a single bout of aerobic exercise, its molecular mechanisms have never been adequately addressed. Thus, changes in mitochondrial content rely on a fine tune adjustment between biogenesis and mitophagy. In the current project, we aim to investigate the mechanisms underlying aerobic exercise-induced mitophagy. For doing that, we will use a proteomic approach, associated to bioinformatics analysis, to identify mitophagy-related targets present in skeletal muscle mitochondrial fractions of animals submitted to a single bout of aerobic exercise. We will use immunoprecipitation and immunoblotting experiments to validate the identified targets, and then perform loss of function experiments both in vitro and in vivo to explore the physiological role of these targets. Additionaly, we will investigate the relationship between mitochondrial biogenesis and mitophagy in exercised skeletal muscles through evaluation of Parkin/PARIS/PGC-1±1 pathway. Hence, we propose that mitophagy may emerge as potential target to modulate oxidative capacity aiming the treatment and/or prevention of metabolic diseases. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
KELAHMETOGLU, YILDIZ; JANNIG, PAULO R.; CERVENKA, IGOR; KOCH, LAUREN G.; BRITTON, STEVEN L.; ZHOU, JIAJIA; WANG, HUATING; ROBINSON, MATTHEW M.; NAIR, K. SREEKUMARAN; RUAS, JORGE L.. Comparative Analysis of Skeletal Muscle Transcriptional Signatures Associated With Aerobic Exercise Capacity or Response to Training in Humans and Rats. FRONTIERS IN ENDOCRINOLOGY, v. 11, . (14/26797-5)

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