Estimation and comparison of lysosomal and cytoplasmic pH of human fibroblasts from healthy donors and patients with lysosomal storage diseases.

Measurements were made of the pH of cytoplasm and lysosomes of cultured skin fibroblasts from healthy donors and from patients with lysosomal storage diseases (mannosidosis, Fabry's disease, and Krabbe's disease), and the effects of sucrose loading on normal fibroblasts were studied. The cytoplasmic pH of the pathological cells did not differ from control values, but the intralysosomal pH was significantly higher in sucrose-loaded normal fibroblasts and in cells from a patient with mannosidosis and from another with Fabry's disease. The change in pH observed accorded with an increase in size of the organelles, owing to accumulation of nonhydrolyzable compounds. In fibroblasts from a patient with Krabbe's disease, which do not store nonhydrolyzable compounds, there was no increase either in intralysosomal pH or in lysosome size. It is suggested that the decrease in the pH difference between the cytoplasm and lysosomes in the pathological cells leads to inhibition of catabolic processes in lysosomes and to some changes in the intracellular transport of these vesicles.