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

    Research output: Contribution to journalArticle

    29 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

    Cite this

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    title = "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. Cell Death and Differentiation (2012) 19, 406-415; doi: 10.1038/cdd.2011.104; published online 2 September 2011",
    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",
    author = "E. Pourkarimi and Sebastian Greiss and A. Gartner",
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    doi = "10.1038/cdd.2011.104",
    language = "English",
    volume = "19",
    pages = "406--415",
    journal = "Cell Death & Differentiation",
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    }

    Evidence that CED-9/Bcl2 and CED-4/Apaf-1 localization is not consistent with the current model for C. elegans apoptosis induction. / Pourkarimi, E.; Greiss, Sebastian; Gartner, A.

    In: Cell Death & Differentiation, Vol. 19, No. 3, 03.2012, p. 406-415.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Evidence that CED-9/Bcl2 and CED-4/Apaf-1 localization is not consistent with the current model for C. elegans apoptosis induction

    AU - Pourkarimi, E.

    AU - Greiss, Sebastian

    AU - Gartner, A.

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    N2 - 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

    AB - 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

    KW - CED-4

    KW - Apaf-1

    KW - CED-9

    KW - Bcl-2

    KW - C. elegans

    KW - apoptosis

    KW - PROGRAMMED CELL-DEATH

    KW - BCL-2-LIKE PROTEIN CED-9

    KW - DAMAGE-INDUCED APOPTOSIS

    KW - CAENORHABDITIS-ELEGANS

    KW - MITOCHONDRIAL-MEMBRANE

    KW - CED-4-CED-9 COMPLEX

    KW - EGL-1

    KW - TRANSLOCATION

    KW - ACTIVATION

    KW - CHECKPOINT

    U2 - 10.1038/cdd.2011.104

    DO - 10.1038/cdd.2011.104

    M3 - Article

    VL - 19

    SP - 406

    EP - 415

    JO - Cell Death & Differentiation

    JF - Cell Death & Differentiation

    SN - 1350-9047

    IS - 3

    ER -