Electron transport chain defect and inefficient respiration may underlie pulmonary hypertension syndrome (ascites)-associated mitochondrial dysfunction in broilers.

By using a series of chemical inhibitors of mitochondrial respiration, a site-specific defect in the electron transport chain was identified in mitochondria obtained from broilers with pulmonary hypertension syndrome (PHS; ascites). Located at the succinate:ubiquinone oxido-reductase (Complex II:CoQ) interface, this defect would allow electrons to leak from the respiratory chain and consume oxygen by forming reactive oxygen species at a greater rate than in control mitochondria. Lower levels of the primary antioxidants, alpha- and beta-tocopherol, and glutathione (GSH) in PHS mitochondria confirmed the presence of oxidative stress. Respiration studies of PHS liver mitochondria also revealed disease-associated decreases in the respiratory control ratio (RCR, an index of electron transport chain coupling). Differences in the RCR as well as the adenosine diphosphate (ADP) to O ratio (an index of oxidative phosphorylation) between control and PHS mitochondria were accentuated by sequential additions of ADP to isolated mitochondria. In a second experiment, similar improvements in functional indices following sequential additions of ADP and responses to respiratory chain inhibitors were observed in liver mitochondria isolated from Single Comb White Leghorn (SCWL) males (resistant to PHS) similar to that observed in control broiler mitochondria in Experiment 1. The combined results indicate the presence of a site-specific defect at either Complex II, ubiquinone, or both in liver mitochondria obtained from broilers with PHS that may be responsible for the oxidative stress and mitochondrial dysfunction observed in this costly metabolic disease.