Abstract
Introduction: Reduced mitochondrial ATP production capacity is likely to contribute to exercise limitation in COPD. It is unknown whether this is attributable to a COPD-specific impairment in intrinsic mitochondrial function(Mitofunc),a reduction in mitochondrial mass(Mitomass),a reduction in mitochondrial number(Mitonumb) or a combination.
Method and Results: 20 COPD [6 male, age 70 (1) years, FEV1 56 (4)%] and 10 healthy controls(HC),[5 male, age 71 (2) years,FEV1 113(6)%)] completed maximal cardio-pulmonary exercise testing (CPET) to determine peak oxygen consumption (VO2), and a resting micro-biopsy of the Vastus Lateralis muscle. Intrinsic Mitofunc was assessed bio-luminometrically in isolated mitochondria as the maximal rate of ATP production (MAPR;using glutamate and succinate as substrates) and normalisation using maximal citrate synthase (CS) activity, Mitomass was CS activity/muscle total protein content and mtDNA relative copy number was an index of Mitonumb.
Table 1. CPET and mitochondrial data | ||
OLDER HC (n=10) | COPD (n=20) | |
Peak VO2 ml/kg/min | 29.7 (1.3) | 24.0* (1.7) |
Intrinsic Mitofunc umol ATP/mmol CS activity | 1235 (193) | 1148 (147) |
Mitomass mmol CS activity/g protein | 0.184 (0.013) | 0.140* (0.011) |
Mitonumb mtDNA copy number relative to gDNA | 631 (70) | 525 (35) |
*Independent Student's T-test (p <0.05) |
Values represent mean(SEM)
Conclusion: Intrinsic mitofunc was not lower in COPD patients compared to HC volunteers and mitonumb were similar between groups. However, mitomass and peak VO2 were lower in COPD. Mitochondrial function is therefore not impaired in skeletal muscle of COPD patients, but they are deconditioned. This points to the utility of endurance exercise training as a therapeutic intervention.
- Copyright ©the authors 2016