Hexokinases inhibit death receptor–dependent apoptosis on the mitochondria
Abstract: Death receptor–mediated apoptosis requires the mitochondrial apoptosis pathway in many mammalian cells. In response to death receptor signaling, the truncated BH3-only protein BID can activate the proapoptotic BCL-2 proteins BAX and BAK and trigger the permeabilization of the mitochondria. BAX and BAK are inhibited by prosurvival BCL-2 proteins through retrotranslocation from the mitochondria into the cytosol, but a specific resistance mechanism to truncated BID-dependent apoptosis is unknown. Here, we report that hexokinase 1 and hexokinase 2 inhibit the apoptosis activator truncated BID as well as the effectors BAX and BAK by retrotranslocation from the mitochondria into the cytosol. BCL-2 protein shuttling and protection from TRAIL- and FasL-induced cell death requires mitochondrial hexokinase localization and interactions with the BH3 motifs of BCL-2 proteins but not glucose phosphorylation. Together, our work establishes hexokinase-dependent retrotranslocation of truncated BID as a selective protective mechanism against death receptor–induced apoptosis on the mitochondria
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Proceedings of the National Academy of Sciences of the United States of America. - 118, 33 (2021) , e2021175118, ISSN: 1091-6490
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2021
- Creator
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Lauterwasser, Joachim
Fimm-Todt, Franziska
Oelgeklaus, Aline
Schreiner, Annabell
Funk, Kathrin
Falquez-Medina, Hugo
Klesse, Ramona
Jahreis, Günther
Zerbes, Ralf Michael
O'Neill, Katelyn
Laan, Martin van der
Luo, Xu
Edlich, Frank
- DOI
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10.1073/pnas.2021175118
- URN
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urn:nbn:de:bsz:25-freidok-2201014
- Rights
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Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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25.03.2025, 1:55 PM CET
Data provider
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Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Lauterwasser, Joachim
- Fimm-Todt, Franziska
- Oelgeklaus, Aline
- Schreiner, Annabell
- Funk, Kathrin
- Falquez-Medina, Hugo
- Klesse, Ramona
- Jahreis, Günther
- Zerbes, Ralf Michael
- O'Neill, Katelyn
- Laan, Martin van der
- Luo, Xu
- Edlich, Frank
- Universität
Time of origin
- 2021
Other Objects (12)
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How Do Hexokinases Inhibit Receptor-Mediated Apoptosis?
Ring-substituted 1-hydroxynaphthalene-2-carboxanilides inhibit proliferation and trigger mitochondria-mediated apoptosis
Regulation of death receptor-induced apoptosis by c-FLIP in pancreatic carcinoma
Mitochondria as triggers and executors of cell death
The interplay between pro-death and pro-survival signaling pathways converging at mitochondria in myocardial ischemia, reperfusion : apoptosis meets autophagy
XIAP-targeting drugs re-sensitize PIK3CA-mutated colorectal cancer cells for death receptor-induced apoptosis
MACC1 regulates death receptor mediated apoptosis in solid cancers through STAT1/3 – Mcl-1 signaling
Identification and characterization of miRNA-133b as a novel regulator of death receptor mediated apoptosis
Identification and characterization of miRNA-133b as a novel regulator of death receptor mediated apoptosis
Alpha-synuclein prevents the formation of spherical mitochondria and apoptosis under oxidative stress
Induction of apoptosis in human cancer cells by targeting mitochondria with gold nanoparticles
The deubiquitinase Usp27x as a novel regulator of cFLIPL protein expression and sensitizer to death-receptor-induced apoptosis
How Do Hexokinases Inhibit Receptor-Mediated Apoptosis?
Ring-substituted 1-hydroxynaphthalene-2-carboxanilides inhibit proliferation and trigger mitochondria-mediated apoptosis
Regulation of death receptor-induced apoptosis by c-FLIP in pancreatic carcinoma
Mitochondria as triggers and executors of cell death
The interplay between pro-death and pro-survival signaling pathways converging at mitochondria in myocardial ischemia, reperfusion : apoptosis meets autophagy
XIAP-targeting drugs re-sensitize PIK3CA-mutated colorectal cancer cells for death receptor-induced apoptosis
MACC1 regulates death receptor mediated apoptosis in solid cancers through STAT1/3 – Mcl-1 signaling
Identification and characterization of miRNA-133b as a novel regulator of death receptor mediated apoptosis
Identification and characterization of miRNA-133b as a novel regulator of death receptor mediated apoptosis
Alpha-synuclein prevents the formation of spherical mitochondria and apoptosis under oxidative stress
Induction of apoptosis in human cancer cells by targeting mitochondria with gold nanoparticles