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

Anton Gartner (1) , Ehsan Pourkarimi (1) , Sebastian Greiss (1)

1 Welcome Trust Centre for Gene Regulation and Expression

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 while the Bcl-2 homolog CED-9 prevents apoptosis. Mammalian Bcl-2 inhibits apoptosis by preventing the release of the Apaf-1 activator cytochome 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.

Mots clés: CED-4; Apaf-1; ced-9; Bcl-2; C. elegans apoptosis

Domaines: Biologie cellulaire

Anton Gartner, Ehsan Pourkarimi, Sebastian Greiss. Evidence that CED-9/Bcl2 and CED-4/Apaf-1 localization is not consistent with the current model for C. elegans apoptosis induction.. Cell Death and Differentiation, 2011, ⟨10.1038/cdd.2011.104⟩. ⟨hal-00675788⟩