Caspase-8 Induces Lysosome-Associated Cell Death in Cancer Cells.

ABSTRACT: Caspase-8, a well-characterized initiator of apoptosis, has also been found to play non-apoptotic roles in cells. In this study, we reveal that caspase-8 can induce cell death in a special way, which does not depend on activation of caspases and mitochondrial initiation. Instead, we prove that caspase-8 can cause lysosomal deacidification and thus lysosomal membrane permeabilization. V-ATPase is a multi-subunit proton pump that acidifies the lumen of lysosome. Our results demonstrate that caspase-8 can bind to the V₀ domain of lysosomal Vacuolar H⁺-ATPase (V-ATPase), but not the V₁ domain, to block the assembly of functional V-ATPase and alkalinize lysosomes. We further demonstrate that the C-terminal of caspase-8 is mainly responsible for the interaction w

SUBMITTER: Zhong B 

PROVIDER: S-EPMC7132614 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature