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ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY

Functional coupling of adenine nucleotide translocase and mitochondrial creatine kinase is enhanced after exercise training in lung transplant skeletal muscle

¹Laboratoire de Bioénergétique Fondamentale et Appliquée, Institut National de la Santé et de la Recherche Médicale E221, Université Joseph Fourier, Grenoble, France; ²Laboratoire d’Exploration Fonctionnelle Cardio-Respiratoire, ³Laboratoire de Pathologie Cellulaire, and ⁴Service de Chirurgie Cardiaque, Centre Hospitalier Universitaire de Grenoble, France; ⁵Genexpress, Génomique Fonctionnelle et Biologie des Systèmes pour la Santé LGN, UMR 7091, Centre National de la Recherche Scientifique et Université Pierre et Marie Curie, Paris, France; ⁶Département de Médecine Aiguë Spécialisée, Centre Hospitalier Universitaire de Grenoble, France

Submitted 1 April 2005 ; accepted in final form 26 May 2005

Mechanisms responsible for limitation of exercise capacity in lung transplant recipients (LR) and benefits gained by exercise training were studied. Mitochondrial respiration parameters, energy transfer, and cell structure were assessed in vastus lateralis biopsies using the permeabilized fiber technique with histochemical and morphometric measurements. Twelve male controls (C) and 12 LR performed exercise training over 12 wk. Before exercise training, there were strong correlations between exercise capacity (maximal O₂ consumption and endurance time at 70% maximal power output) and cellular events, as assessed by percentage of type I fibers and apparent K_m for exogenous ADP. Anticalcineurins were not involved in LR exercise limitation, since there were no differences in maximal mitochondrial rate of respiration before exercise training and no abnormalities in respiratory chain complexes compared with C. Training resulted in a significant increase in physiological parameters both at the cellular (apparent K_m for exogenous ADP and stimulating effect of creatine) and integrated (maximal O₂ consumption, power output at ventilatory threshold, maximal power output, and endurance time at 70% maximal power output) levels in LR and C. After the training period, improvements in maximal O₂ consumption and in maximal mitochondrial rate of respiration were noted, as well as changes in endurance time and percentage of type I fibers. Because there were no changes in diameters and fiber types, baseline alteration of apparent K_m for exogenous ADP and its improvement after training might be related to changes within the intracellular energetic units. After the training period, intracellular energetic units exhibited a higher control of mitochondrial respiration by creatine linked to a more efficient functional coupling adenine nucleotide translocase-mitochondrial creatine kinase, resulting in better exercise performances in C and LR.

mitochondria; oxidative phosphorylation; creatine/phosphocreatine shuttle; pulmonary transplantation; rehabilitation