Altered skeletal muscle respiration in patients with COPD: mitochondrial density or dysfunction?

Abstract

INTRODUCTIONWe sought to determine if the blunted mitochondrial respiration typically observed in the skeletal muscle of patients with chronic obstructive pulmonary disease (COPD) is solely related to changes in mitochondrial density or if qualitative changes in respiration occur.METHODSCombinations of substrates (malate, glutamate, succinate, and ADP) and inhibitors (oligomycin) were used to measure complex I (CI) and complex II (CII) driven state 3 respiration separately and in combination in permeabilized muscle fibers from the vastus lateralis of 9 healthy controls (67±2 years) and 11 COPD patients (FEV1= 56±6%; 63±3 years). State 4 respiration and citrate synthase (CS) activity were measured using these same fibers.RESULTSCompared to controls COPD patients had blunted CI driven state 3 respiration (37.2±4.1, 23.7±2.7 nM/min/mg, respectively) and blunted state 3 respiration with CI and CII (47.2±5.1, 33.7±3.8 nM/min/mg, respectively) (P<0.05) while state 3 driven by CII alone was similar between groups. CS activity and state 4 respiration were not different between groups.CONCLUSIONSGiven that CS activity, an indicator of density, was similar between groups, the blunted respiratory capacity in these COPD patients appears to be related to an attenuation of CI driven respiration. These data indicate that COPD results in qualitative changes in mitochondrial respiration of skeletal muscle.