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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) |
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