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

E. Pourkarimi, Sebastian Greiss, A. Gartner

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    30 Citations (Scopus)

    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. Cell Death and Differentiation (2012) 19, 406-415; doi: 10.1038/cdd.2011.104; published online 2 September 2011

    Original languageEnglish
    Pages (from-to)406-415
    Number of pages10
    JournalCell Death & Differentiation
    Volume19
    Issue number3
    DOIs
    Publication statusPublished - Mar 2012

    Keywords

    • CED-4
    • Apaf-1
    • CED-9
    • Bcl-2
    • C. elegans
    • apoptosis
    • PROGRAMMED CELL-DEATH
    • BCL-2-LIKE PROTEIN CED-9
    • DAMAGE-INDUCED APOPTOSIS
    • CAENORHABDITIS-ELEGANS
    • MITOCHONDRIAL-MEMBRANE
    • CED-4-CED-9 COMPLEX
    • EGL-1
    • TRANSLOCATION
    • ACTIVATION
    • CHECKPOINT

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