气候变化领域集成服务门户(CCPortal): Hexokinases inhibit death receptor-dependent apoptosis on the mitochondria

CCPortal

DOI	10.1073/pnas.2021175118
	Hexokinases inhibit death receptor-dependent apoptosis on the mitochondria
	Lauterwasser J.; Fimm-Todt F.; Oelgeklaus A.; Schreiner A.; Funk K.; Falquez-Medina H.; Klesse R.; Jahreis G.; Zerbes R.M.; O'Neill K.; van der Laan M.; Luo X.; Edlich F.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:33
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Apoptosis; BCL-2 proteins; BH3-only proteins
语种	英语
scopus关键词	BH3 protein; death receptor; Fas ligand; glucose; hexokinase 1; hexokinase 2; hexokinase inhibitor; protein Bak; protein Bax; protein bcl 2; tumor necrosis factor related apoptosis inducing ligand; unclassified drug; antiinfective agent; antineoplastic antibiotic; BAK1 protein, human; BAX protein, human; cyclosporine; dactinomycin; doxorubicin; enzyme inhibitor; Fas ligand; FASLG protein, human; hexokinase; protein Bak; protein Bax; TNFSF10 protein, human; tumor necrosis factor related apoptosis inducing ligand; apoptosis; Article; controlled study; cytosol; gene translocation; human; human cell; mitochondrion; nucleocytoplasmic transport; protection; protein localization; protein motif; protein phosphorylation; apoptosis; cell line; drug effect; gene deletion; gene expression regulation; genetics; metabolism; mitochondrion; physiology; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Apoptosis; bcl-2 Homologous Antagonist-Killer Protein; bcl-2-Associated X Protein; Cell Line; Cyclosporine; Dactinomycin; Doxorubicin; Enzyme Inhibitors; Fas Ligand Protein; Gene Deletion; Gene Expression Regulation, Enzymologic; Hexokinase; Humans; Mitochondria; TNF-Related Apoptosis-Inducing Ligand
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251067
作者单位	Institute for Biochemistry and Molecular Biology, Faculty of Medicine, University of Freiburg, Freiburg, 79104, Germany; Veterinary Physiological Chemical Institute, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, 04103, Germany; Spemann Graduate School of Biology and Medicine, Freiburg, 79104, Germany; Faculty of Biology, University of Freiburg, Freiburg, 79104, Germany; Institute for Biochemistry and Biotechnology, University of Halle, Halle, 06120, Germany; Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, United States; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, United States; Medical Biochemistry and Molecular Biology, Saarland University, Homburg, D-66421, Germany
推荐引用方式 GB/T 7714	Lauterwasser J.,Fimm-Todt F.,Oelgeklaus A.,et al. Hexokinases inhibit death receptor-dependent apoptosis on the mitochondria[J],2021,118(33).
APA	Lauterwasser J..,Fimm-Todt F..,Oelgeklaus A..,Schreiner A..,Funk K..,...&Edlich F..(2021).Hexokinases inhibit death receptor-dependent apoptosis on the mitochondria.Proceedings of the National Academy of Sciences of the United States of America,118(33).
MLA	Lauterwasser J.,et al."Hexokinases inhibit death receptor-dependent apoptosis on the mitochondria".Proceedings of the National Academy of Sciences of the United States of America 118.33(2021).