Portal de Periódicos da CAPES

Prodigiosins Uncouple Mitochondrial and Bacterial F-ATPases: Evidence for Their H+/Cl- Symport Activity

1998; Oxford University Press; Volume: 124; Issue: 3 Linguagem: Inglês

10.1093/oxfordjournals.jbchem.a022147

1756-2651

Hiroki Konno, Hideki Matsuya, Masanori Okamoto, Tomohiko Sato, Y Tanaka, Ken Yokoyama, Takao Kataoka, Kenichiro Nagai, Harry H. Wasserman, S. Ohkuma,

Metabolomics and Mass Spectrometry Studies

Prodigiosin, metacycloprodigiosin, and prodigiosin 25-C all inhibited the acidification activity of submitochondrial and bacterial (Escherichia coli) F-ATPases (FoF1-ATPases) strongly (IC50 =20–30 and 24–30 pmol/mg protein, respectively), without affecting significantly the ATP hydrolysis activity. Their effect on the acidification activity was rapid and reversible, showing non-competitive apparent K1 values of the order of nM to sub-nM. However, unlike FCCP (an ordinary uncoupler of oxidative phosphorylation), they showed no protonophoric activity, as demonstrated by the absence of acceleration of ATP hydrolysis. Prodigiosins also inhibited the acidification of proteoliposomes reconstituted from phospholipids and purified F-ATPase of E. coli, suggesting that their acidification-inhibitory effect is not due to the inhibition of anion channels. They did not, however, inhibit the ATP-dependent formation of membrane potential of F-ATPase vesicles. Furthermore, they inhibited and quickly reversed acidification by F-ATPase only in the presence of chloride, and not in the presence of gluconate anion. Finally, they induced swelling of liposomes and submitochondrial particles in isotonic solution of ammonium chloride but not ammonium gluconate, suggesting that intravesicular entry of Cl− is promoted by prodigiosins. These results suggest that prodigiosins uncouple F-ATPases through promotion of H+/Cl- symport (or OH−/Cl− exchange) across vesicular membranes.