دورية أكاديمية
Diverting CERT-mediated ceramide transport to mitochondria triggers Bax-dependent apoptosis.
| العنوان: | Diverting CERT-mediated ceramide transport to mitochondria triggers Bax-dependent apoptosis. |
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| المؤلفون: | Jain A; Molecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, Osnabrück D-49076, Germany., Beutel O; Molecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, Osnabrück D-49076, Germany.; Max-Planck-Institute for Molecular Cell Biology and Genetics, Dresden D-01307, Germany., Ebell K; Molecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, Osnabrück D-49076, Germany., Korneev S; Molecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, Osnabrück D-49076, Germany., Holthuis JC; Molecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, Osnabrück D-49076, Germany holthuis@uos.de.; Membrane Biochemistry & Biophysics, Bijvoet Center and Institute of Biomembranes, Utrecht University, Utrecht 3584 CH, The Netherlands. |
| المصدر: | Journal of cell science [J Cell Sci] 2017 Jan 15; Vol. 130 (2), pp. 360-371. Date of Electronic Publication: 2016 Nov 25. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Company of Biologists Country of Publication: England NLM ID: 0052457 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-9137 (Electronic) Linking ISSN: 00219533 NLM ISO Abbreviation: J Cell Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge : Company of Biologists Original Publication: London. |
| مواضيع طبية MeSH: | Apoptosis*, Ceramides/*metabolism , Mitochondria/*metabolism , Protein Serine-Threonine Kinases/*metabolism , bcl-2-Associated X Protein/*metabolism, Biocatalysis ; Biological Transport ; Endoplasmic Reticulum/metabolism ; HeLa Cells ; Humans ; Protein Binding ; Protein Transport ; Vesicular Transport Proteins/metabolism ; bcl-2 Homologous Antagonist-Killer Protein/metabolism |
| مستخلص: | A deregulation of ceramide biosynthesis in the endoplasmic reticulum (ER) is frequently linked to induction of mitochondrial apoptosis. Although in vitro studies suggest that ceramides might initiate cell death by acting directly on mitochondria, their actual contribution to the apoptotic response in living cells is unclear. Here, we have analyzed the consequences of targeting the biosynthetic flow of ceramides to mitochondria using a ceramide transfer protein (encoded by COL4A3BP) equipped with an OMM anchor, mitoCERT. Cells expressing mitoCERT import ceramides into mitochondria and undergo Bax-dependent apoptosis. Apoptosis induction by mitoCERT was abolished through (i) removal of its ceramide transfer domain, (ii) disruption of its interaction with VAMP-associated proteins (VAPs) in the ER, (iii) addition of antagonistic CERT inhibitor HPA12, (iv) blocking de novo ceramide synthesis and (v) targeting of a bacterial ceramidase to mitochondria. Our data provide the first demonstration that translocation of ER ceramides to mitochondria specifically commits cells to death and establish mitoCERT as a valuable new tool to unravel the molecular principles underlying ceramide-mediated apoptosis. (© 2017. Published by The Company of Biologists Ltd.) |
| فهرسة مساهمة: | Keywords: Bcl-2 proteins; Ceramide transfer protein; Cytochrome c; Endoplasmic reticulum; Membrane contact sites; Mitochondrial apoptosis; VAP receptor |
| المشرفين على المادة: | 0 (Ceramides) 0 (VAPA protein, human) 0 (Vesicular Transport Proteins) 0 (bcl-2 Homologous Antagonist-Killer Protein) 0 (bcl-2-Associated X Protein) EC 2.7.1.- (CERT1 protein, human) EC 2.7.11.1 (Protein Serine-Threonine Kinases) |
| تواريخ الأحداث: | Date Created: 20161127 Date Completed: 20170811 Latest Revision: 20221109 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1242/jcs.194191 |
| PMID: | 27888218 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1477-9137 |
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| DOI: | 10.1242/jcs.194191 |