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HMGB1 is a mediator of cuproptosis-related sterile inflammation
Cuproptosis is a recently recognized modality of cell death driven by intracellular copper-dependent mitochondrial stress. However, the mediators of the sterile inflammatory response to cuproptotic death are undetermined. Here, we report that high-mobility group box 1 (HMGB1), a damage-associated mo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534480/ https://www.ncbi.nlm.nih.gov/pubmed/36211458 http://dx.doi.org/10.3389/fcell.2022.996307 |
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author | Liu, Jiao Liu, Yang Wang, Yuan Kang, Rui Tang, Daolin |
author_facet | Liu, Jiao Liu, Yang Wang, Yuan Kang, Rui Tang, Daolin |
author_sort | Liu, Jiao |
collection | PubMed |
description | Cuproptosis is a recently recognized modality of cell death driven by intracellular copper-dependent mitochondrial stress. However, the mediators of the sterile inflammatory response to cuproptotic death are undetermined. Here, we report that high-mobility group box 1 (HMGB1), a damage-associated molecular pattern, is released by cuproptotic cells to initiate inflammation. Mechanically, copper accumulation-induced adenosine triphosphate (ATP) depletion activates AMP-activated protein kinase (AMPK) to promote HMGB1 phosphorylation, resulting in increased extracellular release. In contrast, genetic (using RNAi) or pharmacologic (using dorsomorphin) inhibition of AMPK activation limits cuproptosis and HMGB1 release. Functionally, the ability of HMGB1-deficient cuproptotic cells to promote advanced glycosylation end product-specific receptor (AGER, also known as RAGE)-dependent inflammatory cytokine production is greatly reduced. Thus, HMGB1 is a key immune mediator of cuproptosis-initiated sterile inflammation. |
format | Online Article Text |
id | pubmed-9534480 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95344802022-10-06 HMGB1 is a mediator of cuproptosis-related sterile inflammation Liu, Jiao Liu, Yang Wang, Yuan Kang, Rui Tang, Daolin Front Cell Dev Biol Cell and Developmental Biology Cuproptosis is a recently recognized modality of cell death driven by intracellular copper-dependent mitochondrial stress. However, the mediators of the sterile inflammatory response to cuproptotic death are undetermined. Here, we report that high-mobility group box 1 (HMGB1), a damage-associated molecular pattern, is released by cuproptotic cells to initiate inflammation. Mechanically, copper accumulation-induced adenosine triphosphate (ATP) depletion activates AMP-activated protein kinase (AMPK) to promote HMGB1 phosphorylation, resulting in increased extracellular release. In contrast, genetic (using RNAi) or pharmacologic (using dorsomorphin) inhibition of AMPK activation limits cuproptosis and HMGB1 release. Functionally, the ability of HMGB1-deficient cuproptotic cells to promote advanced glycosylation end product-specific receptor (AGER, also known as RAGE)-dependent inflammatory cytokine production is greatly reduced. Thus, HMGB1 is a key immune mediator of cuproptosis-initiated sterile inflammation. Frontiers Media S.A. 2022-09-21 /pmc/articles/PMC9534480/ /pubmed/36211458 http://dx.doi.org/10.3389/fcell.2022.996307 Text en Copyright © 2022 Liu, Liu, Wang, Kang and Tang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Liu, Jiao Liu, Yang Wang, Yuan Kang, Rui Tang, Daolin HMGB1 is a mediator of cuproptosis-related sterile inflammation |
title | HMGB1 is a mediator of cuproptosis-related sterile inflammation |
title_full | HMGB1 is a mediator of cuproptosis-related sterile inflammation |
title_fullStr | HMGB1 is a mediator of cuproptosis-related sterile inflammation |
title_full_unstemmed | HMGB1 is a mediator of cuproptosis-related sterile inflammation |
title_short | HMGB1 is a mediator of cuproptosis-related sterile inflammation |
title_sort | hmgb1 is a mediator of cuproptosis-related sterile inflammation |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534480/ https://www.ncbi.nlm.nih.gov/pubmed/36211458 http://dx.doi.org/10.3389/fcell.2022.996307 |
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