It is well established that when cystine-depleted cystinotic cells are cultured in cystine-containing medium, they reaccumulate cystine within their lysosomes more rapidly than when cultured in cystine-free medium. This has been a puzzling result, since the lysosome membrane of cystinotic cells is impermeable to cystine. To probe the mechanism of cystine reaccumulation, we have measured reaccumulation in the presence of colchicine, an inhibitor of pinocytosis, or of glutamate, a competitive inhibitor of cystine transport into human fibroblasts. Colchicine had no effect, thus eliminating pinocytosis as a putative mechanism for cystine translocation from the culture medium to the lysosomes. Glutamate, however, strongly inhibited cystine reaccumulation. It is concluded that the true mechanism is as follows. 1. Exogenous cystine crosses the plasma membrane on the cystine-glutamate porter. 2. Cystine is reduced in the cytoplasm by GSH. 3. The cysteine that is generated enters the lysosome, where it becomes cystine by participating in the reduction of cystine residues during intralysosomal proteolysis, or by autoxidation.
Skip Nav Destination
Article navigation
Rapid Communication|
April 01 1990
Mechanism of cystine reaccumulation by cystinotic fibroblasts in vitro
Susan Forster;
Susan Forster
1Cellular Pharmacology Research Group, Department of Biological Sciences, University of Keele, Keele, Staffordshire, ST5 5BG, UK
Search for other works by this author on:
Lynne Scarlett;
Lynne Scarlett
1Cellular Pharmacology Research Group, Department of Biological Sciences, University of Keele, Keele, Staffordshire, ST5 5BG, UK
Search for other works by this author on:
John B. Lloyd
John B. Lloyd
1Cellular Pharmacology Research Group, Department of Biological Sciences, University of Keele, Keele, Staffordshire, ST5 5BG, UK
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
August 14 1989
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© 1990 Plenum Publishing Corporation
1990
Biosci Rep (1990) 10 (2): 225–229.
Article history
Received:
August 14 1989
Citation
Susan Forster, Lynne Scarlett, John B. Lloyd; Mechanism of cystine reaccumulation by cystinotic fibroblasts in vitro. Biosci Rep 1 April 1990; 10 (2): 225–229. doi: https://doi.org/10.1007/BF01116582
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.