RT Journal Article
SR Electronic
T1 Site of ROS production by mitochondria of skeletal muscle of patients with COPD
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p4738
VO 38
IS Suppl 55
A1 Luis Puente-Maestu
A1 Javier de Miguel
A1 Luis Άlvarez-Sala
A1 Alberto Tejedor
A1 Alberto Lázaro
A1 Elena Ojeda
A1 Teresa Gόmez
A1 Alvar Agustí
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p4738.abstract
AB Rationale: Exercise-induced oxidative stress is well documented in patients with chronic obstructive pulmonary disease (COPD).Objective: To study the specific site(s) of reactive oxygen species (ROS) production in the Vastus Lateralis (VL) of COPD patients.Methods: VL biopsies were obtained during lung cancer surgery in 11 COPD (67±7 yrs; FEV1 = 54.1±12pp) and 10 controls (66±10 yrs; FEV1 = 92±13pp). Mitochondrial respiration (V'O2m) and ROS output before and after inhibition with rotenone (complex-I), malonate (complex-II) and antimycin-A (complex-III) were determined in mitochondria and submitochondrial fragments.Results: V'O2m were 2.8±0.7 vs 2.7±0.5 mmol min-1 kg-1 (n.s) and respiratory control rate 7.2±1.5 vs 6.1±1.5; p=0.097 (controls/COPD). H2O2 outputs by mitochondria oxidizing complex-I substrates were 51±6 and 150±35 pmol h-1 mg-1 (p<0.001) respectively or 0.8% and 2.1% of the V'O2m. While antimycin-A greatly increased (×7) H2O2 output both in mitochondria and submitochondrial particles in both groups, rotenone only did it in submitochondrial particles. In mitochondria it instead decreased H2O2 output as it did malonate, both upstream blockers of the electron flux to complex-III.Conclusions: Only the ROS generated at complex-III are secreted by the mitochondria. We interpret that this is due to the spatial orientation of complex-I (towards the matrix) and III towards de intermembrane space), being in the first case largely neutralized by the antioxidant system of the mitochondrial matrix.