Advanced search
Start date
Betweenand
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Exercise reestablishes autophagic flux and mitochondrial quality control in heart failure

Full text
Author(s):
Show less -
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.
Total Authors: 16
Document type: Journal article
Source: AUTOPHAGY; v. 13, n. 8, p. 1304-1317, 2017.
Web of Science Citations: 18
Abstract

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)

FAPESP's process: 10/51906-1 - Mitochondrial bioenergetics, ion transport, redox state and DNA metabolism
Grantee:Alicia Juliana Kowaltowski
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 10/00028-4 - Characterization of mitochondrial fusion and fission in heart failure: effects of exercise training
Grantee:Patricia Chakur Brum
Support Opportunities: Regular Research Grants
FAPESP's process: 09/12349-2 - Characterization of mitochondrial function and dynamics in cardiac dysfunction-induced myocardial infarction in rats
Grantee:Juliane Cruz Campos
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 15/20783-5 - Protein quality control in dysfunctional/atrophic skeletal muscle: role of b2-adrenoceptor
Grantee:Julio Cesar Batista Ferreira
Support Opportunities: Regular Research Grants
FAPESP's process: 12/05765-2 - Contribution of aldehyde dehydrogenase 2 to heart failure development
Grantee:Julio Cesar Batista Ferreira
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 16/01633-5 - BETA2-ADRENOCEPTOR ACTIVATION COUNTERACTS SKELETAL MUSCLE WEAKNESS/WASTING: ROLE OF AUTOPHAGY
Grantee:Juliane Cruz Campos
Support Opportunities: Scholarships abroad - Research Internship - Doctorate