Autophagy and Protein Turnover Signaling in Slow-Twitch Muscle during Exercise

Pagano, Allan; Py, Guillaume; Bernardi, Henri; Candau, Robin; Sanchez, Anthony M. J.

doi:10.1249/mss.0000000000000237

Cited by 81 publications

(95 citation statements)

References 36 publications

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“…Findings from our study indicate that expression of both LC3I and LC3II increases in response to the exercise program, with a significant elevation of the LC3II/I ratio, supporting a possible enhanced number of autophagosomes. However, whether this raise is the consequence of an increased autophagosome formation or a defect in their degradation through the lysosome remains to be elucidated (Pagano et al 2014). To further understand the changes in the markers of autophagy, LC3II measurements should be combined with other markers of autophagy.…”

Section: Discussionmentioning

confidence: 99%

“…Regulation of ULK-1 phosphorylation by feeding has been associated with an activation by AMP-activated protein kinase α in humans (Schwalm et al 2015), and short-term aerobic exercise seems to increase the expression of ULK-1 phosphorylated at Ser 555 (Moller et al 2015). In mice, LC3I is lipidated in response to running exercise, and this is accompanied by decreased ULK-1 Ser 757 phosphorylation (Pagano et al 2014). The decreased expression in the autophagy-inhibitory Ser 757 phosphorylated ULK-1 described in the current study supports the notion of an exercise-induced autophagic stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…The first one is the Atg12/Atg5/Atg16 complex, which is essential for the formation of the autophagosome membrane (Walczak and Martens 2013). Other two complexes containing the unc-51-like kinase (ULK-1) and the Bcl-2-interacting protein (beclin)-1 also contribute to promote this initial assembly (Pagano et al 2014). The second step involves the microtubule-associated protein 1 light chain 3 (LC3).…”

Section: Introductionmentioning

confidence: 99%

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Effects of aerobic training on markers of autophagy in the elderly

Mejías-Peña

Rodriguez‐Miguelez

Fernandez‐Gonzalo

et al. 2016

AGE

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Autophagy is a molecular process essential for the maintenance of cellular homeostasis, which appears to (i) decline with age and (ii) respond to physical exercise. In addition, recent evidence suggests a crosstalk between autophagy and toll-like receptor (TLR)-associated inflammatory responses. This study assessed the effects of aerobic exercise training on autophagy and TLR signaling in older subjects. Twentynine healthy women and men (age, 69.7 ± 1.0 year) were randomized to a training (TG) or a control (CG) group. TG performed an 8-week aerobic training program, while CG followed their daily routines. Peripheral blood mononuclear cells were isolated from blood samples obtained before and after the intervention, and protein levels of protein 1 light chain 3 (LC3), sequestosome 1 (p62/SQSTM1), beclin-1, phosphorylated unc-51-like kinase (ULK-1), ubiquitin-like autophagy-related (Atg)12, Atg16, and lysosome-associated membrane protein (LAMP)-2 were measured. TLR2 and TLR4 signaling pathways were also analyzed. Peak oxygen uptake increased in TG after the intervention. Protein expression of beclin-1, Atg12, Atg16, and the LC3II/I ratio increased following the training program (p < 0.05), while expression of p62/SQSTM1 and phosphorylation of ULK-1 at Ser 757 were lower (p < 0.05). Protein content of TLR2, TLR4, myeloid differentiation primary response gen 88 (MyD88), and TIR domaincontaining adaptor-inducing interferon (TRIF) were not significantly modified by exercise. The current data indicate that aerobic exercise training induces alterations in multiple markers of autophagy, which seem to be unrelated to changes in TLR2 and TLR4 signaling pathways. These results expand knowledge on exerciseinduced autophagy adaptations in humans and suggest that the exercise type employed may be a key factor explaining the potential relationship between autophagy and TLR pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of aerobic training on markers of autophagy in the elderly

Mejías-Peña

Rodriguez‐Miguelez

Fernandez‐Gonzalo

et al. 2016

AGE

View full text Add to dashboard Cite

show abstract

“…Endurance exercise training can induce autophagy, and, appropriately, intracellular energetic stress elicited by exercise seems to be the nexus for autophagy induction, as ultra-endurance exercise (Jamart et al, 2012a,b), running to exhaustion (Pagano et al, 2014;Vainshtein et al, 2015b) and exercise commenced when fasted (Jamart et al, 2013;Møller et al, 2015) all upregulate autophagic signalling processes. However, in well-trained human skeletal muscle there is no synergistic effect of prior fasting on autophagy signalling compared with commencing the exercise bout in the fed state, with exercise intensity mitigating the largest autophagic response to contraction (Schwalm et al, 2015).…”

Section: Reduced Energy Availabilitymentioning

confidence: 99%

Effects of skeletal muscle energy availability on protein turnover responses to exercise

Smiles

Hawley

Camera

2016

Journal of Experimental Biology

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Skeletal muscle adaptation to exercise training is a consequence of repeated contraction-induced increases in gene expression that lead to the accumulation of functional proteins whose role is to blunt the homeostatic perturbations generated by escalations in energetic demand and substrate turnover. The development of a specific 'exercise phenotype' is the result of new, augmented steady-state mRNA and protein levels that stem from the training stimulus (i.e. endurance or resistance based). Maintaining appropriate skeletal muscle integrity to meet the demands of training (i.e. increases in myofibrillar and/or mitochondrial protein) is regulated by cyclic phases of synthesis and breakdown, the rate and turnover largely determined by the protein's half-life. Cross-talk among several intracellular systems regulating protein synthesis, breakdown and folding is required to ensure protein equilibrium is maintained. These pathways include both proteasomal and lysosomal degradation systems (ubiquitin-mediated and autophagy, respectively) and the protein translational and folding machinery. The activities of these cellular pathways are bioenergetically expensive and are modified by intracellular energy availability (i.e. macronutrient intake) and the 'training impulse' (i.e. summation of the volume, intensity and frequency). As such, exercisenutrient interactions can modulate signal transduction cascades that converge on these protein regulatory systems, especially in the early post-exercise recovery period. This review focuses on the regulation of muscle protein synthetic response-adaptation processes to divergent exercise stimuli and how intracellular energy availability interacts with contractile activity to impact on muscle remodelling.

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“…These findings occurred with concomitant increases in the expression of UPS components, in particular atrogin-1, MuRF-1, and PSMA1, although the activity of the 26S proteasome itself was interestingly repressed after exercise (71). Laboratory animal studies have also demonstrated a more pronounced upregulation in autophagy-lysosomal gene expression and associated FOXOrelated activity when endurance exercise is performed in the fasted state compared with the fed state (69), particularly in slow-twitch muscle fibers (70), although these findings have not been confirmed in human muscle. Results from our laboratory confirm the effects of endurance exercise on UPSmediated proteolysis, as atrogin-1 and MuRF-1 expression were upregulated during recovery from moderate endurance exercise in recreationally active individuals (72).…”

Section: Exercise and Nutritional Modulation Of Skeletal Muscle Protementioning

confidence: 99%

Assessment of skeletal muscle proteolysis and the regulatory response to nutrition and exercise

Pasiakos

Carbone

2014

IUBMB Life

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Skeletal muscle proteolysis is highly regulated, involving complex intramuscular proteolytic systems that recognize and degrade muscle proteins, and recycle free amino acid precursors for protein synthesis and energy production. Autophagylysosomal, calpain, and caspase systems are contributors to muscle proteolysis, although the ubiquitin proteasome system (UPS) is the primary mechanism by which actomyosin fragments are degraded in healthy muscle. The UPS is sensitive to mechanical force and nutritional deprivation, as recent reports have demonstrated increased proteolytic gene expression and activity of the UPS in response to resistance and endurance exercise, and short-term negative energy balance. However, consuming dietary protein alone (or free amino acids), or as a primary component of a mixed meal, may attenuate intramuscular protein loss by down-regulating proteolytic gene expression and the catabolic activity of the UPS. Although these studies provide novel insight regarding the intramuscular regulation of skeletal muscle mass, the role of proteolysis in the regulation of skeletal muscle protein turnover in healthy human muscle is not well described. This article provides a contemporary review of the intramuscular regulation of skeletal muscle proteolysis in healthy muscle, methodological approaches to assess proteolysis, and highlights the effects of nutrition and exercise on skeletal muscle proteolysis.

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Autophagy and Protein Turnover Signaling in Slow-Twitch Muscle during Exercise

Abstract: These results fit with a regulation of protein breakdown triggered by FoxO3a and Ulk1 pathways after AMPK activation and Akt/MTOR inhibition. Furthermore, our data suggest that mitochondrial fission is quickly increased, and mitochondrial fusion is unchanged during exercise.

Cited by 81 publications

References 36 publications

Effects of aerobic training on markers of autophagy in the elderly

Effects of aerobic training on markers of autophagy in the elderly

Effects of skeletal muscle energy availability on protein turnover responses to exercise

Assessment of skeletal muscle proteolysis and the regulatory response to nutrition and exercise

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