Evidence that CED-9/Bcl2 and CED-4/Apaf-1 localization is not consistent with the current model for C. elegans apoptosis induction.

Abstract

In C. elegans, the BH3-only domain protein EGL-1, the Apaf-1 homolog CED-4 and the CED-3 caspase are required for apoptosis induction, whereas the Bcl-2 homolog CED-9 prevents apoptosis. Mammalian B-cell lymphoma 2 (Bcl-2) inhibits apoptosis by preventing the release of the Apaf-1 (apoptotic protease-activating factor 1) activator cytochrome c from mitochondria. In contrast, C. elegans CED-9 is thought to inhibit CED-4 by sequestering it at the outer mitochondrial membrane by direct binding. We show that CED-9 associates with the outer mitochondrial membrane within distinct foci that do not overlap with CED-4, which is predominantly perinuclear and does not localize to mitochondria. CED-4 further accumulates in the perinuclear space in response to proapoptotic stimuli such as ionizing radiation. This increased accumulation depends on EGL-1 and is abrogated in ced-9 gain-of-function mutants. CED-4 accumulation is not sufficient to trigger apoptosis execution, even though it may prime cells for apoptosis. Our results suggest that the cell death protection conferred by CED-9 cannot be solely explained by a direct interaction with CED-4.

• Authors: E Pourkarimi, S Greiss, A Gartner
• Journal: Cell death and differentiation (Cell Death Differ) Vol. 19 Issue 3 Pg. 406-15 (Mar 2012) ISSN: 1476-5403 [Electronic] England
• PMID: 21886181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptotic Protease-Activating Factor 1
• Caenorhabditis elegans Proteins
• Calcium-Binding Proteins
• Ced-4 protein, C elegans
• Ced-9 protein, C elegans
• Proto-Oncogene Proteins c-bcl-2

Topics

• Animals
• Apoptosis (physiology, radiation effects)
• Apoptotic Protease-Activating Factor 1 (genetics, metabolism)
• Caenorhabditis elegans (genetics, metabolism)
• Caenorhabditis elegans Proteins (genetics, metabolism)
• Calcium-Binding Proteins (genetics, metabolism)
• Mitochondria (genetics, metabolism)
• Mitochondrial Membranes (metabolism)
• Models, Biological
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Radiation, Ionizing