Lysosomal cystine augments apoptosis and causes the phenotype in cystinosis.

ABSTRACT

Nephropathic cystinosis is a lethal inborn error of metabolism that destroys kidney function by age 10 years. It is characterized by lysosomal cystine accumulation. How the cystine causes the phenotype is an open question. We propose that during apoptosis, permeablized lysosomes permit cystine to reach the cytosol where mixed disulfide formation occurs, augmenting apoptosis by interaction with a variety of pro-apoptotic proteins.