ATP-dependent lysosomal cystine efflux is defective in cystinosis.

Lysosomes containing large amounts of the amino acid, cystine, were obtained from transformed, cultured, human lymphoblasts which had been exposed to cystine dimethyl ester. Lysosomal cystine efflux was greatly enhanced by exogenous ATP in cell lines from normal individuals. Cystine efflux was unresponsive to ATP in lysosomes from individuals with the disorder, cystinosis. Efflux of cystine from normal cell lysosomes was inhibited by both the ATP analog, 5-adenylylimidodiphosphate, and the proton translocator, carbonyl cyanide m-chlorophenylhydrazone. Efflux was not affected by ouabain or oligomycin. Thus, lysosomal cystine efflux is dependent upon the functioning of a proton-pump ATPase. ATPase-dependent cystine efflux appears to be aberrant in cystinotic cell lysosomes.