Hexokinases inhibit death receptor–dependent apoptosis on the mitochondria

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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

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Proceedings of the National Academy of Sciences of the United States of America. - 118, 33 (2021) , e2021175118, ISSN: 1091-6490

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2021
Urheber
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
10.1073/pnas.2021175118
URN
urn:nbn:de:bsz:25-freidok-2201014
Rechteinformation
Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
14.08.2025, 10:50 MESZ

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