Insertion of Bax into lysosomal membranes promotes release of lysosomal proteases during apoptosis
(English)Manuscript (preprint) (Other academic)
Bax, a pro-apoptotic Bcl-2 family member, was found to translocate to both mitochondria and lysosames in human fibroblasts during apoptosis induced by staurosporine or naphthazarin. Bax has been shown to insert into tbe outer mitochondrial membrane and promate release of cytochrome c to tbe cytosol. We show translocation of catbepsin D from lysosornes to the cytosol early in apoptosis. Furthermore, inhibition of cathepsin D activity protected from death, suggesting that lysosamal release is an important event in apoptosis. To investigate the mechanism underlying this release, subcellular localisation of Bax was studied. Lysosames were labelled by endocytotic uptake of Texas Red®-conjugated dextran and Bax was visualised by immunostaining or transfection with GFP-Bax. By confocal microscopy, Bax was found to localise to lysosames during apoptosis. Moreover, we demonstrate that recombinant Bax inserts into membranes of isolated rat liver lysosames and indnces release of the lysosamal proteases catbepsins B and D, and N-acetyl-ß-glucoseaminidase. These findings provide a possible explanation for how lysosamal proteases are released to tbe cytosol during apoptosis.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-84474OAI: oai:DiVA.org:liu-84474DiVA: diva2:559450