Insoluble disulfide cross-linked polypeptides accumulate in the functionally compromised lysosomes of fibroblasts treated with the cysteine protease inhibitor E-64

Fergus J. Doherty, Natasha U. Osborn, Julie A. Wassell, Lajos Laszlo, R. John Mayer

Research output: Contribution to journalArticle

8 Citations (Scopus)


Mouse fibroblasts (3T3-L1 cells) accumulate pulse-labeled long-lived polypeptides in detergent- and salt-insoluble aggregates when chased in the presence of inhibitors of lysosomal cysteine cathepsins, including E-64. Proteins found in the detergent- and salt-insoluble fraction include polypeptides which are disulfide cross-linked. E-64-induced polypeptide aggregates cofractionate with lysosomal enzyme markers on density gradients and are found in multivesicular dense bodies which by electron microscopy appear to be engaged in microautophagy. The results are discussed in relation to the possible role of polypeptide aggregation in the sequestration or trapping of cytoplasmic proteins by the lysosomal system.

Original languageEnglish
Pages (from-to)506-518
Number of pages13
JournalExperimental Cell Research
Issue number2
Publication statusPublished - Dec 1989


ASJC Scopus subject areas

  • Cell Biology

Cite this