Lack of Activation of Mitophagy during Endurance Exercise in Human

Schwalm, Céline; Deldicque, Louise; Francaux, Marc

doi:10.1249/mss.0000000000001256

Cited by 31 publications

(26 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Endurance training increases markers of basal autophagy in skeletal muscle of mice [31] . Acute endurance exercise bouts have been found to stimulate autophagy and mitophagy in skeletal muscle of trained [32] , [33] , [34] and untrained humans [40] , but, until now, the impact of endurance-training remained unclear. Our present findings suggest that basal autophagy is not elevated in skeletal muscle of endurance-trained humans.…”

Section: Discussionmentioning

confidence: 99%

“…Chronic endurance exercise training leads to increased markers of basal autophagy and mitophagy in murine skeletal muscle [29] , [31] . Meanwhile, single bouts of endurance exercise stimulate mitophagy in a fed state-dependent manner in endurance-trained human skeletal muscle in the absence of autophagy activation [32] . When the same endurance exercise bout was completed following a fast, the onset of mitophagy activation was delayed [32] .…”

Section: Introductionmentioning

confidence: 99%

“…Meanwhile, single bouts of endurance exercise stimulate mitophagy in a fed state-dependent manner in endurance-trained human skeletal muscle in the absence of autophagy activation [32] . When the same endurance exercise bout was completed following a fast, the onset of mitophagy activation was delayed [32] . Ultra-endurance exercise, when conducted in a fed state, has been shown to increase markers of both autophagy and mitophagy activity in endurance-trained human skeletal muscle [33] , [34] .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Skeletal muscle autophagy and mitophagy in endurance-trained runners before and after a high-fat meal

Tarpey

Davy

McMillan

et al. 2017

Molecular Metabolism

View full text Add to dashboard Cite

ObjectiveWe tested the hypothesis that skeletal muscle of endurance-trained male runners would exhibit elevated autophagy and mitophagy markers, which would be associated with greater metabolic flexibility following a high-fat meal (HFM).MethodsMuscle biopsies were collected to determine differences in autophagy and mitophagy protein markers and metabolic flexibility under fasting conditions and 4 h following a HFM between endurance-trained male runners (n = 10) and sedentary, non-obese controls (n = 9).ResultsMaximal oxygen consumption (ml·kg·min−1) was approximately 50% higher (p < 0.05) in endurance-trained runners compared with sedentary controls (65.8 ± 2.3 and 43.1 ± 3.4, respectively). Autophagy markers were similar between groups. Mitophagy and mitochondrial dynamics protein markers were significantly higher in skeletal muscle of endurance-trained runners compared with sedentary controls in the fasted state, although unaffected by the HFM. Skeletal muscle metabolic flexibility was similar between groups when fasted (p > 0.05), but increased in response to the HFM in endurance-trained athletes only (p < 0.005). Key mitophagy markers, phospho-Pink1Thr257 and phospho-ParkinS65 (r = 0.64, p < 0.005), and phospo-ParkinSer65 and phospho-Drp1Ser616 (r = 0.70, p < 0.05) were correlated only within the endurance-trained group. Autophagy and mitophagy markers were not correlated with metabolic flexibility.ConclusionIn summary, mitophagy may be enhanced in endurance-trained runners based on elevated markers of mitophagy and mitochondrial dynamics. The HFM did not alter autophagy or mitophagy in either group. The absence of a relationship between mitophagy markers and metabolic flexibility suggests that mitophagy is not a key determinant of metabolic flexibility in a healthy population, but further investigation is warranted.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Skeletal muscle autophagy and mitophagy in endurance-trained runners before and after a high-fat meal

Tarpey

Davy

McMillan

et al. 2017

Molecular Metabolism

View full text Add to dashboard Cite

show abstract

“…In our study, cardiomyocytes possess high level of oxidative capacity and the enhanced mitophagy may be independent of Bnip3/Nix. But cycling for 2 h at 70% maximal oxygen uptake intensity upregulated Bnip3 and Nix levels in human skeletal muscle (Schwalm et al 2017). It seems that a bout of exercise rather than endurance exercise training upregulates Bnip3/Nix signaling.…”

Section: Discussionmentioning

confidence: 96%

Exercise training and dietary restriction affect PINK1/Parkin and Bnip3/Nix-mediated cardiac mitophagy in mice

Zhao¹,

Zhu²,

Song³

et al. 2018

gpb

View full text Add to dashboard Cite

The aim of this study was to investigate the effects of exercise training and dietary restriction on cardiac PINK1/Parkin and Bnip3/Nix pathways involved in mitophagy. C57BL/6 mice were assigned to control (C), exercise training (T), dietary restriction (D) and exercise training + dietary restriction (TD) groups. T group undertook 10 weeks of swimming training. D group was subjected to 40% food reduction. TD group undertook the combination of exercise training and food reduction. Suspectable mitophagy autophagosomes can be observed in T and D groups and more autophagosomes appeared in TD group. In T group, both PINK1 mRNA and protein levels increased significantly (p < 0.01) but Bnip3 and Nix expressions decreased significantly (p < 0.05). Dietary restriction resulted in elevation of Drp1 (p < 0.01) and reduction and Nix (p < 0.05) in D group. The load in TD group resulted in serious mitochondrial abnormalities and myofibrillar damages accompanied by increases in PINK1 and Drp1 levels (p < 0.01) and decreases in Bnip3 and Nix levels (p < 0.05). The increase in PINK1 expression (exercise protocol) or Drp1 expression (diet protocol) contributes to cardiac activation of mitophagy, whereas Bnip3 and Nix are not implicated in this activation.

show abstract

“…Instead, we found a central autophagy marker, total-ULK1 (Call et al, 2017 ), significantly upregulated after training, yet a lower level of phospho-ULK1 Ser317 in relation to the total-ULK1. It is under debate whether repeated post exercise mitophagy activation is necessary to induce long term training adaptations (Møller et al, 2015 ; Schwalm et al, 2017 ). Although it has been shown that both resistance and endurance training increase mitophagy of peripheral blood mononuclear cells in elderly people (Mejías-Peña et al, 2016 , 2017 ), mitophagy in muscle tissue may act through a different mechanism.…”

Section: Discussionmentioning

confidence: 99%

Resistance Training with Co-ingestion of Anti-inflammatory Drugs Attenuates Mitochondrial Function

et al. 2017

View full text Add to dashboard Cite

Aim: The current study aimed to examine the effects of resistance exercise with concomitant consumption of high vs. low daily doses of non-steroidal anti-inflammatory drugs (NSAIDs) on mitochondrial oxidative phosphorylation in skeletal muscle. As a secondary aim, we compared the effects of eccentric overload with conventional training.Methods: Twenty participants were randomized to either a group taking high doses (3 × 400 mg/day) of ibuprofen (IBU; 27 ± 5 year; n = 11) or a group ingesting a low dose (1 × 75 mg/day) of acetylsalicylic acid (ASA; 26 ± 4 year; n = 9) during 8 weeks of supervised knee extensor resistance training. Each of the subject's legs were randomized to complete the training program using either a flywheel (FW) device emphasizing eccentric overload, or a traditional weight stack machine (WS). Maximal mitochondrial oxidative phosphorylation (CI+IIP) from permeabilized skeletal muscle bundles was assessed using high-resolution respirometry. Citrate synthase (CS) activity was assessed using spectrophotometric techniques and mitochondrial protein content using western blotting.Results: After training, CI+IIP decreased (P < 0.05) in both IBU (23%) and ASA (29%) with no difference across medical treatments. Although CI+IIP decreased in both legs, the decrease was greater (interaction p = 0.015) in WS (33%, p = 0.001) compared with FW (19%, p = 0.078). CS activity increased (p = 0.027) with resistance training, with no interactions with medical treatment or training modality. Protein expression of ULK1 increased with training in both groups (p < 0.001). The increase in quadriceps muscle volume was not correlated with changes in CI+IIP (R = 0.16).Conclusion: These results suggest that 8 weeks of resistance training with co-ingestion of anti-inflammatory drugs reduces mitochondrial function but increases mitochondrial content. The observed changes were not affected by higher doses of NSAIDs consumption, suggesting that the resistance training intervention was the prime mediator of the decreased mitochondrial phosphorylation. Finally, we noted that flywheel resistance training, emphasizing eccentric overload, rescued some of the reduction in mitochondrial function seen with conventional resistance training.

show abstract

Lack of Activation of Mitophagy during Endurance Exercise in Human

Cited by 31 publications

References 42 publications

Skeletal muscle autophagy and mitophagy in endurance-trained runners before and after a high-fat meal

Skeletal muscle autophagy and mitophagy in endurance-trained runners before and after a high-fat meal

Exercise training and dietary restriction affect PINK1/Parkin and Bnip3/Nix-mediated cardiac mitophagy in mice

Resistance Training with Co-ingestion of Anti-inflammatory Drugs Attenuates Mitochondrial Function

Contact Info

Product

Resources

About