Perfluorooctane sulfonamide: A structurally novel uncoupler of oxidative phosphorylation

Rick G. Schnellmann, Randall O. Manning

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)344-348
Number of pages5
JournalBBA - Bioenergetics
Volume1016
Issue number3
DOIs
StatePublished - Apr 26 1990
Externally publishedYes

Keywords

  • Oxidative phosphorylation
  • Perfluorooctane sulfonamide
  • Sulfluramid
  • Uncoupler

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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