title: Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle.
abstract: Mitochondrial proteins such as uncoupling protein 3 (UCP3) and adenine nucleotide translocase (ANT) may mediate back-leakage of protons and serve as uncouplers of oxidative phosphorylation. We hypothesized that UCP3 and ANT increase after prolonged exercise and/or endurance training, resulting in increased uncoupled respiration (UCR). Subjects were investigated with muscle biopsies before and after acute exercise (75 min of cycling at 70% of .VO2peak) or 6 weeks endurance training. Mitochondria were isolated and respiration measured in the absence (UCR or state 4) and presence of ADP (coupled respiration or state 3). Protein expression of UCP3 and ANT was measured with Western blotting. After endurance training, .VO2peak, citrate synthase activity (CS), state 3 respiration and ANT increased by 24, 47, 40 and 95%, respectively (all P < 0.05), whereas UCP3 remained unchanged. When expressed per unit of CS (a marker of mitochondrial volume) UCP3 and UCR decreased by 54% and 18%(P < 0.05). CS increased by 43% after acute exercise and remained elevated after 3 h of recovery (P < 0.05), whereas the other muscle parameters remained unchanged. An intriguing finding was that acute exercise reversibly enhanced the capacity of mitochondria to accumulate Ca2+(P < 0.05) before opening of permeability transition pores. In conclusion, UCP3 protein and UCR decrease after endurance training when related to mitochondrial volume. These changes may prevent excessive basal thermogenesis. Acute exercise enhances mitochondrial resistance to Ca2+ overload but does not influence UCR or protein expression of UCP3 and ANT. The increased Ca2+ resistance may prevent mitochondrial degradation and the mechanism needs to be further explored.
authors.affiliation: Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark. ksahlin@health.sdu.dk
authors.forename: Maria
authors.initials: M
authors.lastname: Fernström
authors.forename: Michail
authors.initials: M
authors.lastname: Tonkonogi
authors.forename: Kent
authors.initials: K
authors.lastname: Sahlin
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000328:Adult; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D008931:Mitochondria, Muscle / Q000502:physiology*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000502:physiology*; D010101:Oxygen Consumption; D010806:Physical Education and Training; D010807:Physical Endurance; D013997:Time Factors; D000071247:Uncoupling Protein 3
chemical_list: D002352:Carrier Proteins; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3; D000244:Adenosine Diphosphate; D000226:Mitochondrial ADP, ATP Translocases; D002950:Citrate (si)-Synthase; D002118:Calcium