The mitochondrial fission protein hFis1 requires the endoplasmic reticulum gateway to induce apoptosis.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72773
Title:
The mitochondrial fission protein hFis1 requires the endoplasmic reticulum gateway to induce apoptosis.
Authors:
Alirol, Emilie; James, Dominic I; Huber, Denise; Marchetto, Andrea; Vergani, Lodovica; Martinou, Jean-Claude; Scorrano, Luca
Abstract:
Mitochondrial fission ensures organelle inheritance during cell division and participates in apoptosis. The fission protein hFis1 triggers caspase-dependent cell death, by causing the release of cytochrome c from mitochondria. Here we show that mitochondrial fission induced by hFis1 is genetically distinct from apoptosis. In cells lacking the multidomain proapoptotic Bcl-2 family members Bax and Bak (DKO), hFis1 caused mitochondrial fragmentation but not organelle dysfunction and apoptosis. Similarly, a mutant in the intermembrane region of hFis1-induced fission but not cell death, further dissociating mitochondrial fragmentation from apoptosis induction. Selective correction of the endoplasmic reticulum (ER) defect of DKO cells restored killing by hFis1, indicating that death by hFis1 relies on the ER gateway of apoptosis. Consistently, hFis1 did not directly activate BAX and BAK, but induced Ca(2+)-dependent mitochondrial dysfunction. Thus, hFis1 is a bifunctional protein that independently regulates mitochondrial fragmentation and ER-mediated apoptosis.
Affiliation:
Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, I-35129 Padova, Italy.
Citation:
The mitochondrial fission protein hFis1 requires the endoplasmic reticulum gateway to induce apoptosis. 2006, 17 (11):4593-605 Mol. Biol. Cell
Journal:
Molecular Biology of the Cell
Issue Date:
Nov-2006
URI:
http://hdl.handle.net/10541/72773
DOI:
10.1091/mbc.E06-05-0377
PubMed ID:
16914522
Type:
Article
Language:
en
ISSN:
1059-1524
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorAlirol, Emilie-
dc.contributor.authorJames, Dominic I-
dc.contributor.authorHuber, Denise-
dc.contributor.authorMarchetto, Andrea-
dc.contributor.authorVergani, Lodovica-
dc.contributor.authorMartinou, Jean-Claude-
dc.contributor.authorScorrano, Luca-
dc.date.accessioned2009-07-07T12:07:05Z-
dc.date.available2009-07-07T12:07:05Z-
dc.date.issued2006-11-
dc.identifier.citationThe mitochondrial fission protein hFis1 requires the endoplasmic reticulum gateway to induce apoptosis. 2006, 17 (11):4593-605 Mol. Biol. Cellen
dc.identifier.issn1059-1524-
dc.identifier.pmid16914522-
dc.identifier.doi10.1091/mbc.E06-05-0377-
dc.identifier.urihttp://hdl.handle.net/10541/72773-
dc.description.abstractMitochondrial fission ensures organelle inheritance during cell division and participates in apoptosis. The fission protein hFis1 triggers caspase-dependent cell death, by causing the release of cytochrome c from mitochondria. Here we show that mitochondrial fission induced by hFis1 is genetically distinct from apoptosis. In cells lacking the multidomain proapoptotic Bcl-2 family members Bax and Bak (DKO), hFis1 caused mitochondrial fragmentation but not organelle dysfunction and apoptosis. Similarly, a mutant in the intermembrane region of hFis1-induced fission but not cell death, further dissociating mitochondrial fragmentation from apoptosis induction. Selective correction of the endoplasmic reticulum (ER) defect of DKO cells restored killing by hFis1, indicating that death by hFis1 relies on the ER gateway of apoptosis. Consistently, hFis1 did not directly activate BAX and BAK, but induced Ca(2+)-dependent mitochondrial dysfunction. Thus, hFis1 is a bifunctional protein that independently regulates mitochondrial fragmentation and ER-mediated apoptosis.en
dc.language.isoenen
dc.subject.meshAdenosine Triphosphatases-
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshCell Respiration-
dc.subject.meshDNA Mutational Analysis-
dc.subject.meshEndoplasmic Reticulum-
dc.subject.meshFibroblasts-
dc.subject.meshHumans-
dc.subject.meshMembrane Proteins-
dc.subject.meshMice-
dc.subject.meshMitochondria-
dc.subject.meshMitochondrial Membranes-
dc.subject.meshMitochondrial Proteins-
dc.subject.meshPermeability-
dc.subject.meshProtein Structure, Tertiary-
dc.subject.meshReactive Oxygen Species-
dc.subject.meshbcl-2 Homologous Antagonist-Killer Protein-
dc.subject.meshbcl-2-Associated X Protein-
dc.titleThe mitochondrial fission protein hFis1 requires the endoplasmic reticulum gateway to induce apoptosis.en
dc.typeArticleen
dc.contributor.departmentDulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, I-35129 Padova, Italy.en
dc.identifier.journalMolecular Biology of the Cellen

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