DOI: 10.1083/jcb.200207071. Mitochondrial release of apoptosis-inducing factor occurs downstream of cytochrome <i>c</i> release in response to several proapoptotic stimuli

Mitochondrial release of apoptosis-inducing factor occurs downstream of cytochrome c release in response to several proapoptotic stimuli

10.1083/jcb.200207071

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

Mitochondrial outer membrane permeabilization by proapoptotic Bcl-2 family proteins, such as Bax, plays a crucial role in apoptosis induction. However, whether this only causes the intracytosolic release of inducers of caspase-dependent death, such as cytochrome c, or also of caspase-independent death, such as apoptosis-inducing factor (AIF) remains unknown. Here, we show that on isolated mitochondria, Bax causes the release of cytochrome c, but not of AIF, and the association of AIF with the mitochondrial inner membrane provides a simple explanation for its lack of release upon Bax-mediated outer membrane permeabilization. In cells overexpressing Bax or treated either with the Bax- or Bak-dependent proapoptotic drugs staurosporine or actinomycin D, or with hydrogen peroxide, caspase inhibitors did not affect the intracytosolic translocation of cytochrome c, but prevented that of AIF. These results provide a paradigm for mitochondria-dependent death pathways in which AIF cannot substitute for caspase executioners because its intracytosolic release occurs downstream of that of cytochrome c.

Bibliography

Arnoult, D., Parone, P., Martinou, J.-C., Antonsson, B., Estaquier, J., & Ameisen, J. C. (2002). Mitochondrial release of apoptosis-inducing factor occurs downstream of cytochrome c release in response to several proapoptotic stimuli. The Journal of Cell Biology, 159(6), 923â929.

Authors 6

Damien Arnoult (first)
Philippe Parone (additional)
Jean-Claude Martinou (additional)
Bruno Antonsson (additional)
Jérôme Estaquier (additional)
Jean Claude Ameisen (additional)

References 20 Referenced 258

10.1042/bj3450271 / Biochem. J. (2000)
10.1083/jcb.144.5.891 / J. Cell Biol. (1999)
10.1083/jcb.143.1.217 / J. Cell Biol. (1998)
10.1126/science.281.5381.1317 / Science. (1998)
10.1074/jbc.274.4.2225 / J. Biol. Chem. (1999)
10.1038/35004029 / Nat. Cell Biol. (2000)
10.1038/35069004 / Nature. (2001)
10.1073/pnas.95.9.4997 / Proc. Natl. Acad. Sci. USA. (1998)
10.1038/nature01034 / Nature. (2002)
10.1074/jbc.M003807200 / J. Biol. Chem. (2000)
{'key': '2023072214010621400_BIB11', 'first-page': '63', 'volume': '2', 'year': '2001', 'journal-title': 'Nat. Rev. Mol. Cell Biol.'} / Nat. Rev. Mol. Cell Biol. (2001)
10.1083/jcb.121.6.1233 / J. Cell Biol. (1993)
10.4049/jimmunol.167.3.1222 / J. Immunol. (2001)
10.1038/17135 / Nature. (1999)
10.1038/sj.cdd.4400966 / Cell Death Differ. (2002)
10.1101/gad.14.16.2060 / Genes Dev. (2000)
10.1126/science.1059108 / Science. (2001)
10.1182/blood.V94.5.1683 / Blood. (1999)
10.1126/science.1072221 / Science. (2002)
10.1038/35048073 / Nat. Rev. Mol. Cell Biol. (2001)

Dates

Type	When
Created	22 years, 8 months ago (Dec. 23, 2002, 2:43 p.m.)
Deposited	2 years, 1 month ago (July 22, 2023, 10:01 a.m.)
Indexed	1 month, 3 weeks ago (July 7, 2025, 1:45 a.m.)
Issued	22 years, 8 months ago (Dec. 16, 2002)
Published	22 years, 8 months ago (Dec. 16, 2002)
Published Online	22 years, 8 months ago (Dec. 16, 2002)
Published Print	22 years, 8 months ago (Dec. 23, 2002)

Funders 0

None

BibTeX

@article{Arnoult_2002, title={Mitochondrial release of apoptosis-inducing factor occurs downstream of cytochrome c release in response to several proapoptotic stimuli}, volume={159}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200207071}, DOI={10.1083/jcb.200207071}, number={6}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Arnoult, Damien and Parone, Philippe and Martinou, Jean-Claude and Antonsson, Bruno and Estaquier, Jérôme and Ameisen, Jean Claude}, year={2002}, month=dec, pages={923–929} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        7
      ]
    ],
    "date-time": "2025-07-07T05:45:10Z",
    "timestamp": 1751867110392
  },
  "reference-count": 20,
  "publisher": "Rockefeller University Press",
  "issue": "6",
  "content-domain": {
    "domain": [
      "rupress.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2002,
        12,
        23
      ]
    ]
  },
  "abstract": "<jats:p>Mitochondrial outer membrane permeabilization by proapoptotic Bcl-2 family proteins, such as Bax, plays a crucial role in apoptosis induction. However, whether this only causes the intracytosolic release of inducers of caspase-dependent death, such as cytochrome c, or also of caspase-independent death, such as apoptosis-inducing factor (AIF) remains unknown. Here, we show that on isolated mitochondria, Bax causes the release of cytochrome c, but not of AIF, and the association of AIF with the mitochondrial inner membrane provides a simple explanation for its lack of release upon Bax-mediated outer membrane permeabilization. In cells overexpressing Bax or treated either with the Bax- or Bak-dependent proapoptotic drugs staurosporine or actinomycin D, or with hydrogen peroxide, caspase inhibitors did not affect the intracytosolic translocation of cytochrome c, but prevented that of AIF. These results provide a paradigm for mitochondria-dependent death pathways in which AIF cannot substitute for caspase executioners because its intracytosolic release occurs downstream of that of cytochrome c.</jats:p>",
  "DOI": "10.1083/jcb.200207071",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        12,
        23
      ]
    ],
    "date-time": "2002-12-23T19:43:29Z",
    "timestamp": 1040672609000
  },
  "page": "923-929",
  "update-policy": "http://dx.doi.org/10.1083/jcb.crossmarkpolicy",
  "source": "Crossref",
  "is-referenced-by-count": 258,
  "title": "Mitochondrial release of apoptosis-inducing factor occurs downstream of cytochrome <i>c</i> release in response to several proapoptotic stimuli",
  "prefix": "10.1083",
  "volume": "159",
  "author": [
    {
      "given": "Damien",
      "family": "Arnoult",
      "sequence": "first",
      "affiliation": [
        {
          "name": "1EMI-U 9922 Institut National de la Sante\u0301 et de la Recherche Medicale (INSERM)/Universite\u0301 Paris 7, IFR02, AP-HP, CHU Bichat, 75018 Paris, France"
        }
      ]
    },
    {
      "given": "Philippe",
      "family": "Parone",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "2Department of Cell Biology, University of Geneva, 1211 Geneva 4, Switzerland"
        }
      ]
    },
    {
      "given": "Jean-Claude",
      "family": "Martinou",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "2Department of Cell Biology, University of Geneva, 1211 Geneva 4, Switzerland"
        }
      ]
    },
    {
      "given": "Bruno",
      "family": "Antonsson",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "3Serono Pharmaceutical Research Institute, Serono International SA, CH-1228 Plan-les-Ouates, Geneva, Switzerland"
        }
      ]
    },
    {
      "given": "Je\u0301ro\u0302me",
      "family": "Estaquier",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "1EMI-U 9922 Institut National de la Sante\u0301 et de la Recherche Medicale (INSERM)/Universite\u0301 Paris 7, IFR02, AP-HP, CHU Bichat, 75018 Paris, France"
        }
      ]
    },
    {
      "given": "Jean Claude",
      "family": "Ameisen",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "1EMI-U 9922 Institut National de la Sante\u0301 et de la Recherche Medicale (INSERM)/Universite\u0301 Paris 7, IFR02, AP-HP, CHU Bichat, 75018 Paris, France"
        }
      ]
    }
  ],
  "member": "291",
  "published-online": {
    "date-parts": [
      [
        2002,
        12,
        16
      ]
    ]
  },
  "reference": [
    {
      "key": "2023072214010621400_BIB1",
      "doi-asserted-by": "crossref",
      "first-page": "271",
      "DOI": "10.1042/bj3450271",
      "volume": "345",
      "year": "2000",
      "journal-title": "Biochem. J."
    },
    {
      "key": "2023072214010621400_BIB2",
      "doi-asserted-by": "crossref",
      "first-page": "891",
      "DOI": "10.1083/jcb.144.5.891",
      "volume": "144",
      "year": "1999",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072214010621400_BIB3",
      "doi-asserted-by": "crossref",
      "first-page": "217",
      "DOI": "10.1083/jcb.143.1.217",
      "volume": "143",
      "year": "1998",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072214010621400_BIB4",
      "doi-asserted-by": "crossref",
      "first-page": "1317",
      "DOI": "10.1126/science.281.5381.1317",
      "volume": "281",
      "year": "1998",
      "journal-title": "Science."
    },
    {
      "key": "2023072214010621400_BIB5",
      "doi-asserted-by": "crossref",
      "first-page": "2225",
      "DOI": "10.1074/jbc.274.4.2225",
      "volume": "274",
      "year": "1999",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072214010621400_BIB6",
      "doi-asserted-by": "crossref",
      "first-page": "156",
      "DOI": "10.1038/35004029",
      "volume": "2",
      "year": "2000",
      "journal-title": "Nat. Cell Biol."
    },
    {
      "key": "2023072214010621400_BIB7",
      "doi-asserted-by": "crossref",
      "first-page": "549",
      "DOI": "10.1038/35069004",
      "volume": "410",
      "year": "2001",
      "journal-title": "Nature."
    },
    {
      "key": "2023072214010621400_BIB8",
      "doi-asserted-by": "crossref",
      "first-page": "4997",
      "DOI": "10.1073/pnas.95.9.4997",
      "volume": "95",
      "year": "1998",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072214010621400_BIB9",
      "doi-asserted-by": "crossref",
      "first-page": "367",
      "DOI": "10.1038/nature01034",
      "volume": "419",
      "year": "2002",
      "journal-title": "Nature."
    },
    {
      "key": "2023072214010621400_BIB10",
      "doi-asserted-by": "crossref",
      "first-page": "22713",
      "DOI": "10.1074/jbc.M003807200",
      "volume": "275",
      "year": "2000",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072214010621400_BIB11",
      "first-page": "63",
      "volume": "2",
      "year": "2001",
      "journal-title": "Nat. Rev. Mol. Cell Biol."
    },
    {
      "key": "2023072214010621400_BIB12",
      "doi-asserted-by": "crossref",
      "first-page": "1233",
      "DOI": "10.1083/jcb.121.6.1233",
      "volume": "121",
      "year": "1993",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072214010621400_BIB13",
      "doi-asserted-by": "crossref",
      "first-page": "1222",
      "DOI": "10.4049/jimmunol.167.3.1222",
      "volume": "167",
      "year": "2001",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072214010621400_BIB14",
      "doi-asserted-by": "crossref",
      "first-page": "441",
      "DOI": "10.1038/17135",
      "volume": "397",
      "year": "1999",
      "journal-title": "Nature."
    },
    {
      "key": "2023072214010621400_BIB15",
      "doi-asserted-by": "crossref",
      "first-page": "301",
      "DOI": "10.1038/sj.cdd.4400966",
      "volume": "9",
      "year": "2002",
      "journal-title": "Cell Death Differ."
    },
    {
      "key": "2023072214010621400_BIB16",
      "doi-asserted-by": "crossref",
      "first-page": "2060",
      "DOI": "10.1101/gad.14.16.2060",
      "volume": "14",
      "year": "2000",
      "journal-title": "Genes Dev."
    },
    {
      "key": "2023072214010621400_BIB17",
      "doi-asserted-by": "crossref",
      "first-page": "727",
      "DOI": "10.1126/science.1059108",
      "volume": "292",
      "year": "2001",
      "journal-title": "Science."
    },
    {
      "key": "2023072214010621400_BIB18",
      "doi-asserted-by": "crossref",
      "first-page": "1683",
      "DOI": "10.1182/blood.V94.5.1683",
      "volume": "94",
      "year": "1999",
      "journal-title": "Blood."
    },
    {
      "key": "2023072214010621400_BIB19",
      "doi-asserted-by": "crossref",
      "first-page": "259",
      "DOI": "10.1126/science.1072221",
      "volume": "297",
      "year": "2002",
      "journal-title": "Science."
    },
    {
      "key": "2023072214010621400_BIB20",
      "doi-asserted-by": "crossref",
      "first-page": "67",
      "DOI": "10.1038/35048073",
      "volume": "2",
      "year": "2001",
      "journal-title": "Nat. Rev. Mol. Cell Biol."
    }
  ],
  "container-title": "The Journal of Cell Biology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://rupress.org/jcb/article-pdf/159/6/923/1521361/jcb1596923.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://rupress.org/jcb/article-pdf/159/6/923/1521361/jcb1596923.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        7,
        22
      ]
    ],
    "date-time": "2023-07-22T14:01:33Z",
    "timestamp": 1690034493000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://rupress.org/jcb/article/159/6/923/33283/Mitochondrial-release-of-apoptosis-inducing-factor"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2002,
        12,
        16
      ]
    ]
  },
  "references-count": 20,
  "journal-issue": {
    "issue": "6",
    "published-print": {
      "date-parts": [
        [
          2002,
          12,
          23
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1083/jcb.200207071",
  "relation": {
    "has-review": [
      {
        "id-type": "doi",
        "id": "10.3410/f.1011210.178370",
        "asserted-by": "object"
      }
    ]
  },
  "ISSN": [
    "1540-8140",
    "0021-9525"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2002,
        12,
        16
      ]
    ]
  }
}