Mitrochondrial NADH dehydrogenase in cystic fibrosis.

We have shown that skin fibroblast from patients with cystic fibrosis (CF) 
and from carriers for CF [heterozygotes (HZ)] consume more O2 than 
do their controls. When the mitochondrial electron transport inhibitor rotenone was 
added to the cells, the relative inhibition of O2 consumption was 
CF greater than HZ greater than controls (P less than 0.005 
in both comparisons). Because rotenone specifically inhibits NADH dehydrogenase, [NADH: (acceptor) 
oxidoreductase, EC 1.6.99.3], which is the enzyme of energy-conserving site 1 
of the mitochondrial electron transport system, activity and kinetics of this 
enzyme system were studied in fibroblast homogenates. NADH dehydrogenase activity was 
equal in cells from the three genotypes. At pH 8.0, affinity 
of the enzyme for its substrate was CF greater than HZ 
= controls; at pH 8.6, affinity was CF greater than HZ 
= controls (P less than 0.005 for the differences). pH optima 
for the genotypes were without exception 8.6 (CF), 8.3 (HZ), and 
8.0 (control). HZ and control lines were distinguished unequivocally in a 
blind test on the basis of differences in pH optima. Purified 
mitochondrial preparations revealed pH optima identical to those found in whole 
cell homogenates. These data suggest that the mutant gene responsible for 
CF is expressed in the complex mitochondrial NADH dehydrogenase system. 