TY - JOUR
T1 - Perfluorooctane sulfonamide
T2 - A structurally novel uncoupler of oxidative phosphorylation
AU - Schnellmann, Rick G.
AU - Manning, Randall O.
N1 - Funding Information:
This work was supported by a grant from the Veterinary Medical Experiment Station, University of Georgia. R.G.S. is a recipient of a PMA Foundation Faculty Development Award.
PY - 1990/4/26
Y1 - 1990/4/26
N2 - The effects of sulfluramid (N-ethylperfluorooctane sulfonamide) and perfluorooctane sulfonamide (DESFA) on isolated rabbit renal cortical mitochondria (RCM) were examined. Sulfluramid (1-100 μM) and DESFA (0.5-50 μM) increased state 4 respiration of RCM respiring on pyruvate / malate or succinate in a concentration dependent manner in the absence of a phosphate acceptor. In addition, both sulfluramid and DESFA increased state 4 respiration in the presence of oligomycin, an inhibitor of F0F1-ATPase. The effects of sulfluramid (200 μM), DESFA (100 μM), and the known protonophore and uncoupler of oxidative phosphorylation, carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) (1 μM), on RCM proton movement were examined directly by monitoring extramitochondrial pH and indirectly by monitoring passive mitochondrial swelling. Immediately upon addition, DESFA and FCCP, but not sulfluramid, dissipated the RCM proton gradient and caused RCM to swell in solutions of NaCl or NH4Cl. These results show that DESFA uncouples oxidative phosphorylation by acting as a protonophore. RCM were shown to metabolize sulfluramid to DESFA which suggests that the increase in state 4 respiration observed with sulfluramid is due to DESFA. DESFA is unique in that it is one of two uncouplers that does not contain a ring structure and thus may be a useful model in the study of oxidative phosphorylation.
AB - The effects of sulfluramid (N-ethylperfluorooctane sulfonamide) and perfluorooctane sulfonamide (DESFA) on isolated rabbit renal cortical mitochondria (RCM) were examined. Sulfluramid (1-100 μM) and DESFA (0.5-50 μM) increased state 4 respiration of RCM respiring on pyruvate / malate or succinate in a concentration dependent manner in the absence of a phosphate acceptor. In addition, both sulfluramid and DESFA increased state 4 respiration in the presence of oligomycin, an inhibitor of F0F1-ATPase. The effects of sulfluramid (200 μM), DESFA (100 μM), and the known protonophore and uncoupler of oxidative phosphorylation, carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) (1 μM), on RCM proton movement were examined directly by monitoring extramitochondrial pH and indirectly by monitoring passive mitochondrial swelling. Immediately upon addition, DESFA and FCCP, but not sulfluramid, dissipated the RCM proton gradient and caused RCM to swell in solutions of NaCl or NH4Cl. These results show that DESFA uncouples oxidative phosphorylation by acting as a protonophore. RCM were shown to metabolize sulfluramid to DESFA which suggests that the increase in state 4 respiration observed with sulfluramid is due to DESFA. DESFA is unique in that it is one of two uncouplers that does not contain a ring structure and thus may be a useful model in the study of oxidative phosphorylation.
KW - Oxidative phosphorylation
KW - Perfluorooctane sulfonamide
KW - Sulfluramid
KW - Uncoupler
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U2 - 10.1016/0005-2728(90)90167-3
DO - 10.1016/0005-2728(90)90167-3
M3 - Article
C2 - 2331477
AN - SCOPUS:0025317105
SN - 0005-2728
VL - 1016
SP - 344
EP - 348
JO - BBA - Bioenergetics
JF - BBA - Bioenergetics
IS - 3
ER -