Exercise reestablishes autophagic flux and mitochondrial quality control in heart failure

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Campos, Juliane C. ; Queliconi, Bruno B. ; Bozi, Luiz H. M. ; Bechara, Luiz R. G. ; Dourado, Paulo M. M. ; Andres, Allen M. ; Jannig, Paulo R. ; Gomes, Katia M. S. ; Zambelli, Vanessa O. ; Rocha-Resende, Cibele ; Guatimosim, Silvia ; Brum, Patricia C. ; Mochly-Rosen, Daria ; Gottlieb, Roberta A. ; Kowaltowski, Alicia J. ; Ferreira, Julio C. B.

• Tipo de documento: Artigo Científico
• Fonte: AUTOPHAGY; v. 13, n. 8, p. 1304-1317, 2017.
• Citações Web of Science: 18

Resumo

We previously reported that facilitating the clearance of damaged mitochondria through macroautophagy/autophagy protects against acute myocardial infarction. Here we characterize the impact of exercise, a safe strategy against cardiovascular disease, on cardiac autophagy and its contribution to mitochondrial quality control, bioenergetics and oxidative damage in a post-myocardial infarction-induced heart failure animal model. We found that failing hearts displayed reduced autophagic flux depicted by accumulation of autophagy-related markers and loss of responsiveness to chloroquine treatment at 4 and 12 wk after myocardial infarction. These changes were accompanied by accumulation of fragmented mitochondria with reduced O-2 consumption, elevated H2O2 release and increased Ca2+-Cinduced mitochondrial permeability transition pore opening. Of interest, disruption of autophagic flux was sufficient to decrease cardiac mitochondrial function in sham-treated animals and increase cardiomyocyte toxicity upon mitochondrial stress. Importantly, 8 wk of exercise training, starting 4 wk after myocardial infarction at a time when autophagy and mitochondrial oxidative capacity were already impaired, improved cardiac autophagic flux. These changes were followed by reduced mitochondrial number: size ratio, increased mitochondrial bioenergetics and better cardiac function. Moreover, exercise training increased cardiac mitochondrial number, size and oxidative capacity without affecting autophagic flux in sham-treated animals. Further supporting an autophagy mechanism for exercise-induced improvements of mitochondrial bioenergetics in heart failure, acute in vivo inhibition of autophagic flux was sufficient to mitigate the increased mitochondrial oxidative capacity triggered by exercise in failing hearts. Collectively, our findings uncover the potential contribution of exercise in restoring cardiac autophagy flux in heart failure, which is associated with better mitochondrial quality control, bioenergetics and cardiac function. (AU)

• Processo FAPESP: 10/51906-1 - Bioenergética, transporte iônico, balanço redox e metabolismo de DNA em mitocôndrias
• Beneficiário: Alicia Juliana Kowaltowski
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 10/00028-4 - Caracterização dos processos de fusão e fissão de mitocôndria na insuficiência cardíaca: efeitos do treinamento físico aeróbico
• Beneficiário: Patricia Chakur Brum
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/12349-2 - Caracterização da função e da dinâmica mitocondrial em modelo animal de disfunção cardíaca associada ao infarto do miocárdio
• Beneficiário: Juliane Cruz Campos
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 15/20783-5 - Controle de qualidade de proteína na disfunção/atrofia muscular esquelética: papel do receptor ²2- adrenérgico
• Beneficiário: Julio Cesar Batista Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/05765-2 - Contribuição da enzima aldeído desidrogenase 2 na progressão da insuficiência cardíaca
• Beneficiário: Julio Cesar Batista Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 16/01633-5 - Papel protetor da estimulação beta2-adrenérgica na disfunção/atrofia muscular esquelética: contribuição do sistema lisossomal-autofágico
• Beneficiário: Juliane Cruz Campos
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado