دورية أكاديمية
أعرض في EDS

Hyperactivation of SREBP induces pannexin-1-dependent lytic cell death.

التفاصيل البيبلوغرافية
العنوان: Hyperactivation of SREBP induces pannexin-1-dependent lytic cell death.
المؤلفون: Xiong Y; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Taikang Center for Life and Medical Sciences, Taikang Medical School, Wuhan University, Wuhan, China., Luo J; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Taikang Center for Life and Medical Sciences, Taikang Medical School, Wuhan University, Wuhan, China., Hong ZY; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Taikang Center for Life and Medical Sciences, Taikang Medical School, Wuhan University, Wuhan, China., Zhu WZ; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Taikang Center for Life and Medical Sciences, Taikang Medical School, Wuhan University, Wuhan, China., Hu A; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Taikang Center for Life and Medical Sciences, Taikang Medical School, Wuhan University, Wuhan, China., Song BL; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Taikang Center for Life and Medical Sciences, Taikang Medical School, Wuhan University, Wuhan, China. Electronic address: blsong@whu.edu.cn.
المصدر: Journal of lipid research [J Lipid Res] 2024 Jul; Vol. 65 (7), pp. 100579. Date of Electronic Publication: 2024 Jun 14.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 0376606 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1539-7262 (Electronic) Linking ISSN: 00222275 NLM ISO Abbreviation: J Lipid Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 2021- : [New York] : Elsevier
Original Publication: Memphis, Lipid Research, inc.
مواضيع طبية MeSH: Cell Death*/drug effects , Connexins*/metabolism , Connexins*/genetics , Nerve Tissue Proteins*/metabolism , Nerve Tissue Proteins*/genetics , Sterol Regulatory Element Binding Protein 2*/metabolism, Humans ; Caspase 3/metabolism ; Caspase 7/metabolism
مستخلص: Sterol-regulatory element binding proteins (SREBPs) are a conserved transcription factor family governing lipid metabolism. When cellular cholesterol level is low, SREBP2 is transported from the endoplasmic reticulum to the Golgi apparatus where it undergoes proteolytic activation to generate a soluble N-terminal fragment, which drives the expression of lipid biosynthetic genes. Malfunctional SREBP activation is associated with various metabolic abnormalities. In this study, we find that overexpression of the active nuclear form SREBP2 (nSREBP2) causes caspase-dependent lytic cell death in various types of cells. These cells display typical pyroptotic and necrotic signatures, including plasma membrane ballooning and release of cellular contents. However, this phenotype is independent of the gasdermin family proteins or mixed lineage kinase domain-like (MLKL). Transcriptomic analysis identifies that nSREBP2 induces expression of p73, which further activates caspases. Through whole-genome CRISPR-Cas9 screening, we find that Pannexin-1 (PANX1) acts downstream of caspases to promote membrane rupture. Caspase-3 or 7 cleaves PANX1 at the C-terminal tail and increases permeability. Inhibition of the pore-forming activity of PANX1 alleviates lytic cell death. PANX1 can mediate gasdermins and MLKL-independent cell lysis during TNF-induced or chemotherapeutic reagents (doxorubicin or cisplatin)-induced cell death. Together, this study uncovers a noncanonical function of SREBPs as a potentiator of programmed cell death and suggests that PANX1 can directly promote lytic cell death independent of gasdermins and MLKL.
Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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فهرسة مساهمة: Keywords: Pannexin-1; SREBP; apoptosis; cholesterol; gasdermin; hyperactivation; lytic cell death; membrane rupture
المشرفين على المادة: EC 3.4.22.- (Caspase 3)
EC 3.4.22.- (Caspase 7)
0 (Connexins)
0 (Nerve Tissue Proteins)
0 (PANX1 protein, human)
0 (SREBF2 protein, human)
0 (Sterol Regulatory Element Binding Protein 2)
تواريخ الأحداث: Date Created: 20240616 Date Completed: 20240728 Latest Revision: 20240814
رمز التحديث: 20240814
مُعرف محوري في PubMed: PMC11284708
DOI: 10.1016/j.jlr.2024.100579
PMID: 38880128
قاعدة البيانات: MEDLINE
الوصف
تدمد:1539-7262
DOI:10.1016/j.jlr.2024.100579