title: Autophagy is not required to sustain exercise and PRKAA1/AMPK activity but is important to prevent mitochondrial damage during physical activity.
abstract: Physical activity has been recently documented to play a fundamental physiological role in the regulation of autophagy in several tissues. It has also been reported that autophagy is required for exercise itself and for training-induced adaptations in glucose homeostasis. These autophagy-mediated metabolic improvements are thought to be largely dependent on the activation of the metabolic sensor PRKAA1/AMPK. However, it is unknown whether these important benefits stem from systemic adaptations or are due solely to alterations in skeletal muscle metabolism. To address this we utilized inducible, muscle-specific, atg7 knockout mice that we have recently generated. Our findings indicate that acute inhibition of autophagy in skeletal muscle just prior to exercise does not have an impact on physical performance, PRKAA1 activation, or glucose homeostasis. However, we reveal that autophagy is critical for the preservation of mitochondrial function during damaging muscle contraction. This effect appears to be gender specific affecting primarily females. We also establish that basal oxidative stress plays a crucial role in mitochondrial maintenance during normal physical activity. Therefore, autophagy is an adaptive response to exercise that ensures effective mitochondrial quality control during damaging physical activity.
authors.affiliation: a Dulbecco Telethon Institute; Venetian Institute of Molecular Medicine ; Padova , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lo Verso
authors.forename: Silvia
authors.initials: S
authors.lastname: Carnio
authors.forename: Anna
authors.initials: A
authors.lastname: Vainshtein
authors.forename: Marco
authors.initials: M
authors.lastname: Sandri
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D001343:Autophagy / Q000502:physiology*; D000071193:Autophagy-Related Protein 7; D005260:Female; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008928:Mitochondria / Q000502:physiology*; D009119:Muscle Contraction; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal
chemical_list: D000975:Antioxidants; C502661:Atg7 protein, mouse; D008869:Microtubule-Associated Proteins; C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases; D000071193:Autophagy-Related Protein 7; D005947:Glucose
keywords: ACACA, acetyl-CoA carboxylase alpha; AMPK; ATG7, autophagy-related 7; BNIP3, BCL2/adenovirus E1B 19 kDa interacting protein 3; FDB, flexor digitorum brevis; MAP1LC3A, microtubule-associated protein 1 light chain 3; NAC, N-acetylcysteine; PARK2, parkin RBR E3 ubiquitin protein ligase; PRKAA1, protein kinase AMP-activated, alpha 1 catalytic subunit; ROS, reactive oxygen species; SQSTM1, sequestosome 1; TA, tibialis anterior; TMRM, tetramethylrhodamine, methyl ester; autophagy; exercise; metabolism; mitochondria; skeletal muscle