Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/134406
Title: Activation of macroautophagy and chaperone-mediated autophagy in human skeletal muscle by high-intensity exercise in normoxia and hypoxia and after recovery with or without post-exercise ischemia
Authors: Martínez Cantón, Miriam 
Galván Álvarez, Víctor 
Gallego Selles, Ángel 
Gelaber Rebato,Miriam 
Garcia Gonzalez, Eduardo 
González Henríquez, Juan José 
Martín Rincón, Marcos 
Calbet, José A.L. 
UNESCO Clasification: 321311 Fisioterapia
Keywords: Autophagy
Biopsies
Exercise
Fatigue
Hypoxia, et al
Issue Date: 2024
Journal: Free Radical Biology and Medicine 
Abstract: Autophagy is essential for the adaptive response to exercise and physiological skeletal muscle functionality. However, the mechanisms leading to the activation of macroautophagy and chaperone-mediated autophagy in human skeletal muscle in response to high-intensity exercise remain elusive. Our findings demonstrate that macroautophagy and chaperone-mediated autophagy are stimulated by high-intensity exercise in normoxia (PIO2: 143 mmHg) and severe acute hypoxia (PIO2: 73 mmHg) in healthy humans. High-intensity exercise induces macroautophagy initiation through AMPKα phosphorylation, which phosphorylates and activates ULK1. ULK1 phosphorylates BECN1 at Ser15, eliciting the dissociation of BECN1-BCL2 crucial for phagophore formation. Besides, high-intensity exercise elevates the LC3B-II:LC3B–I ratio, reduces total SQSTM1/p62 levels, and induces p-Ser349 SQSTM1/p62 phosphorylation, suggesting heightened autophagosome degradation. PHAF1/MYTHO, a novel macroautophagy biomarker, is highly upregulated in response to high-intensity exercise. The latter is accompanied by elevated LAMP2A expression, indicating chaperone-mediated autophagy activation regardless of post-exercise HSPA8/HSC70 downregulation. Despite increased glycolytic metabolism, severe acute hypoxia does not exacerbate the autophagy signaling response. Signaling changes revert within 1 min of recovery with free circulation, while the application of immediate post-exercise ischemia impedes recovery. Our study concludes that macroautophagy and chaperone-mediated autophagy pathways are strongly activated by high-intensity exercise, regardless of PO2, and that oxygenation is necessary to revert these signals to pre-exercise values. PHAF1/MYTHO emerges as a pivotal exercise-responsive autophagy marker positively associated with the LC3B-II:LC3B–I ratio.
URI: http://hdl.handle.net/10553/134406
ISSN: 0891-5849
DOI: 10.1016/j.freeradbiomed.2024.07.012
Source: Free Radical Biology and Medicine [ISSN 0891-5849], v. 222, p. 607-624, (Septiembre 2024)
Appears in Collections:Artículos
Adobe PDF (11,44 MB)
Show full item record

SCOPUSTM   
Citations

1
checked on Nov 3, 2024

WEB OF SCIENCETM
Citations

1
checked on Nov 3, 2024

Google ScholarTM

Check

Altmetric


Share



Export metadata



Items in accedaCRIS are protected by copyright, with all rights reserved, unless otherwise indicated.