PRODIGIOSIN 25-C UNCOUPLES VACUOLAR-TYPE H+-ATPASE, INHIBITS VACUOLAR ACIDIFICATION AND AFFECTS GLYCOPROTEIN PROCESSING

Prodigiosin 25-C inhibited the accumulation of 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine and acridine orange in the acidic compartments of baby hamster kidney cells with little perturbation of cellular ATP levels. In rat liver lysosomes, prodigiosin 25-C inhibited the proton pump activity with an IC50 of approximately 30 nM, but did not affect ATPase activity up to 1 mu M. It also delayed the transport of vesicular stomatitis virus G protein and induced a drastic swelling of Golgi apparatus and mitochondria. These results indicate that prodigiosin 25-C raises the pH of acidic compartments through inhibition of the proton pump activity of vacuolar type H+-ATPase, thereby causing the functional and morphological changes to the Golgi apparatus.