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Altered skeletal muscle respiration in patients with COPD: mitochondrial density or dysfunction?
Author(s) -
Gifford Jayson Reed,
Garten Ryan S,
Trinity Joel,
Park Songyoung,
Layec Gwenael,
Larsen Steen,
Richardson Russell S
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1209.4
Subject(s) - respiration , copd , oligomycin , medicine , skeletal muscle , endocrinology , mitochondrion , chemistry , biology , biochemistry , anatomy , atpase , enzyme
We 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. METHODS Combinations 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. RESULTS Compared 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. CONCLUSIONS Given 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.