Physical exercise increases autophagic signaling through ULK1 in human skeletal muscle

Møller, Andreas Buch; Vendelbo, Mikkel Holm; Christensen, Britt; Clasen, Berthil Forrest; Bak, Ann Mosegaard; Jørgensen, Jens Otto Lunde; Møller, Niels; Jessen, Niels

doi:10.1152/japplphysiol.01116.2014

Cited by 90 publications

(126 citation statements)

References 32 publications

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“…Thus, phosphorylation of ULK-1 at Ser 555 is an important stimulus of autophagy, whereas phosphorylation at Ser 757 promotes an inhibitory effect (Kim et al 2011). 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).…”

Section: Discussionmentioning

confidence: 99%

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%

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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“…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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“…Autophagy is elevated for around 24 h after exercise (Moller et al 2015). Moreover, baseline levels of autophagy rise in adaptation to repeated bouts of exercise (Lira et al 2013; Grumati et al 2010; Ulbricht et al 2015).…”

Section: Reviewmentioning

confidence: 99%

Disrupted autophagy undermines skeletal muscle adaptation and integrity

Jokl

Blanco

2016

Mamm Genome

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This review assesses the importance of proteostasis in skeletal muscle maintenance with a specific emphasis on autophagy. Skeletal muscle appears to be particularly vulnerable to genetic defects in basal and induced autophagy, indicating that autophagy is co-substantial to skeletal muscle maintenance and adaptation. We discuss emerging evidence that tension-induced protein unfolding may act as a direct link between mechanical stress and autophagic pathways. Mechanistic links between protein damage, autophagy and muscle hypertrophy, which is also induced by mechanical stress, are still poorly understood. However, some mouse models of muscle disease show ameliorated symptoms upon effective targeting of basal autophagy. These findings highlight the importance of autophagy as therapeutic target and suggest that elucidating connections between protein unfolding and mTOR-dependent or mTOR-independent hypertrophic responses is likely to reveal specific therapeutic windows for the treatment of muscle wasting disorders.Electronic supplementary materialThe online version of this article (doi:10.1007/s00335-016-9659-2) contains supplementary material, which is available to authorized users.

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Physical exercise increases autophagic signaling through ULK1 in human skeletal muscle

Cited by 90 publications

References 32 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

Disrupted autophagy undermines skeletal muscle adaptation and integrity

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