Abnormal transition pore kinetics and cytochrome C release in muscle mitochondria of patients with chronic obstructive pulmonary disease

Am J Respir Cell Mol Biol. 2009 Jun;40(6):746-50. doi: 10.1165/rcmb.2008-0289OC. Epub 2008 Nov 14.


Skeletal muscle dysfunction (SMD) is frequent in patients with chronic obstructive pulmonary disease (COPD). Mitochondrial abnormalities appear to play a role in the pathogenesis of SMD. The mitochondrion permeability transition pore (MPTP) facilitates the leakage of mitochondrial matrix constituents, such as cytochrome c (cyto-c), and triggers apoptosis, known to occur in skeletal muscle of patients with COPD. Our objective was to study MPTP kinetics and cyto-c release in skeletal muscle mitochondria of patients with COPD. Mitochondria were isolated from the vastus lateralis (VL), external intercostalis (EI), and latissimus dorsi (LD) in 11 patients with COPD (66 +/- 9 yr; FEV(1) 66 +/- 13%) and 15 smokers with normal lung function (64 +/- 6 yr; FEV(1) 95 +/- 11%) who required thoracic surgery for a localized lung neoplasm. MPTP kinetics were determined spectrophotometrically (time to reach V'max, V'max and mitochondrial swelling) and cyto-c release by enzyme-linked immunosorbent assay. MPTP kinetics and cyto-c release were abnormal in patients with COPD in the three muscles studied. In addition, V'max of VL mitochondria was significantly related (P < 0.01) to BMI (r = -0.75 COPD, -0.67 control) and aerobic capacity (r = -0.70 COPD, -0.60 control) for the COPD group. MPTP kinetics and cyto-c release are abnormal in skeletal and respiratory muscles of patients with moderate COPD, suggesting a systemic mechanism(s) occurring early during the course of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis
  • Cytochromes c / metabolism*
  • Female
  • Humans
  • Kinetics
  • Lung / pathology
  • Male
  • Middle Aged
  • Mitochondria / metabolism*
  • Mitochondria, Muscle / metabolism*
  • Muscle, Skeletal / metabolism
  • Muscles / metabolism*
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Smoking


  • Cytochromes c