title: Modulation of autophagy and ubiquitin-proteasome pathways during ultra-endurance running.
abstract: In this study, the coordinated activation of ubiquitin-proteasome pathway (UPP), autophagy-lysosomal pathway (ALP), and mitochondrial remodeling including mitophagy was assessed by measuring protein markers during ultra-endurance running exercise in human skeletal muscle. Eleven male, experienced ultra-endurance athletes ran for 24 h on a treadmill. Muscle biopsy samples were taken from the vastus lateralis muscle 2 h before starting and immediately after finishing exercise. Athletes ran 149.8 ± 16.3 km with an effective running time of 18 h 42 min ( ± 41 min). The phosphorylation state of Akt (-74 ± 5%; P < 0.001), FOXO3a (-49 ± 9%; P < 0.001), mTOR Ser2448 (-32 ± 14%; P = 0.028), and 4E-BP1 (-34 ± 7%; P < 0.001) was decreased, whereas AMPK phosphorylation state increased by 247 ± 170% (P = 0.042). Proteasome β2 subunit activity increased by 95 ± 44% (P = 0.028), whereas the activities associated with the β1 and β5 subunits remained unchanged. MuRF1 protein level increased by 55 ± 26% (P = 0.034), whereas MAFbx protein and ubiquitin-conjugated protein levels did not change. LC3bII increased by 554 ± 256% (P = 0.005), and the form of ATG12 conjugated to ATG5 increased by 36 ± 17% (P = 0.042). The mitochondrial fission marker phospho-DRP1 increased by 110 ± 47% (P = 0.003), whereas the fusion marker Mfn1 and the mitophagy markers Parkin and PINK1 remained unchanged. These results fit well with a coordinated regulation of ALP and UPP triggered by FOXO3 and AMPK during ultra-endurance exercise.
authors.affiliation: Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: Cécile
authors.initials: C
authors.lastname: Jamart
authors.forename: Marc
authors.initials: M
authors.lastname: Francaux
authors.forename: Guillaume Y
authors.initials: GY
authors.lastname: Millet
authors.forename: Louise
authors.initials: L
authors.lastname: Deldicque
authors.forename: Delphine
authors.initials: D
authors.lastname: Frère
authors.forename: Léonard
authors.initials: L
authors.lastname: Féasson
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D001343:Autophagy; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D018797:Cell Cycle Proteins; D034281:Dynamins; D002149:Energy Intake; D004734:Energy Metabolism; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010807:Physical Endurance; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D052097:Quadriceps Muscle / Q000201:enzymology* / Q000473:pathology*; D012420:Running; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D012694:Serine; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D055372:AMP-Activated Protein Kinases; D048868:Adaptor Proteins, Signal Transducing; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D001786:Blood Glucose; D018797:Cell Cycle Proteins; D034281:Dynamins; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D020558:GTP Phosphohydrolases; D007328:Insulin; D008869:Microtubule-Associated Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; D046988:Proteasome Endopeptidase Complex; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D044843:SKP Cullin F-Box Protein Ligases; D012694:Serine; D025841:Small Ubiquitin-Related Modifier Proteins; D058570:TOR Serine-Threonine Kinases; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C466624:ATG12 protein, human; C502778:ATG5 protein, human; C087000:EIF4EBP1 protein, human; C499517:FOXO3 protein, human; C502070:MAP1LC3B protein, human; C440907:FBXO32 protein, human; C440908:TRIM63 protein, human; C111567:parkin protein; C546842:MTOR protein, human; C561469:PSMB2 protein, human; C088874:PSMB5 protein, human; C061553:ATP dependent 26S protease; C470017:Mfn1 protein, human; C110768:DNM1L protein, human