title: Hypoxia refines plasticity of mitochondrial respiration to repeated muscle work.
abstract: OBJECTIVE
  We explored whether altered expression of factors tuning mitochondrial metabolism contributes to muscular adaptations with endurance training in the condition of lowered ambient oxygen concentration (hypoxia) and whether these adaptations relate to oxygen transfer as reflected by subsarcolemmal mitochondria and oxygen metabolism in muscle.
  
  
  METHODS
  Male volunteers completed 30 bicycle exercise sessions in normoxia or normobaric hypoxia (4,000 m above sea level) at 65% of the respective peak aerobic power output. Myoglobin content, basal oxygen consumption, and re-oxygenation rates upon reperfusion after 8 min of arterial occlusion were measured in vastus muscles by magnetic resonance spectroscopy. Biopsies from vastus lateralis muscle, collected pre and post a single exercise bout, and training, were assessed for levels of transcripts and proteins being associated with mitochondrial metabolism.
  
  
  RESULTS
  Hypoxia specifically lowered the training-induced expression of markers of respiratory complex II and IV (i.e. SDHA and isoform 1 of COX-4; COX4I1) and preserved fibre cross-sectional area. Concomitantly, trends (p < 0.10) were found for a hypoxia-specific reduction in the basal oxygen consumption rate, and improvements in oxygen repletion, and aerobic performance in hypoxia. Repeated exercise in hypoxia promoted the biogenesis of subsarcolemmal mitochondria and this was co-related to expression of isoform 2 of COX-4 with higher oxygen affinity after single exercise, de-oxygenation time and myoglobin content (r ≥ 0.75). Conversely, expression in COX4I1 with training correlated negatively with changes of subsarcolemmal mitochondria (r < -0.82).
  
  
  CONCLUSIONS
  Hypoxia-modulated adjustments of aerobic performance with repeated muscle work are reflected by expressional adaptations within the respiratory chain and modified muscle oxygen metabolism.
authors: Centre de Génétique et de Physiologie Moléculaire et Cellulaire, CNRS UMR 5534, Université Lyon 1, Villeurbanne, France.
authors: Dominique
authors: D
authors: Desplanches
authors: Myriam
authors: M
authors: Amami
authors: Sylvie
authors: S
authors: Dupré-Aucouturier
authors: Paola
authors: P
authors: Valdivieso
authors: Silvia
authors: S
authors: Schmutz
authors: Matthias
authors: M
authors: Mueller
authors: Hans
authors: H
authors: Hoppeler
authors: Roland
authors: R
authors: Kreis
authors: Martin
authors: M
authors: Flück
mesh_terms: D000328:Adult; D000531:Altitude; D016022:Case-Control Studies; D019069:Cell Respiration; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D015444:Exercise; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism* / Q000502:physiology; D009211:Myoglobin / Q000378:metabolism; D010101:Oxygen Consumption; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015424:Reperfusion
chemical_list: D009211:Myoglobin; D012333:RNA, Messenger; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I