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Impairment of Mitochondrial ATP Synthesis Induces RIPK3-dependent Necroptosis in Lung Epithelial Cells During Lung Injury by Lung Inflammation

Dysfunction of mitochondrial metabolism is implicated in cellular injury and cell death. While mitochondrial dysfunction is associated with lung injury by lung inflammation, the mechanism by which the impairment of mitochondrial ATP synthesis regulates necroptosis during acute lung injury (ALI) by l...

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Autores principales: Lee, Su Hwan, Shin, Ju Hye, Park, Min Woo, Kim, Junhyung, Chung, Kyung Soo, Na, Sungwon, Ryu, Ji-Hwan, Lee, Jin Hwa, Park, Moo Suk, Kim, Young Sam, Moon, Jong-Seok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Association of Immunologists 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9066008/
https://www.ncbi.nlm.nih.gov/pubmed/35573150
http://dx.doi.org/10.4110/in.2022.22.e18
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author Lee, Su Hwan
Shin, Ju Hye
Park, Min Woo
Kim, Junhyung
Chung, Kyung Soo
Na, Sungwon
Ryu, Ji-Hwan
Lee, Jin Hwa
Park, Moo Suk
Kim, Young Sam
Moon, Jong-Seok
author_facet Lee, Su Hwan
Shin, Ju Hye
Park, Min Woo
Kim, Junhyung
Chung, Kyung Soo
Na, Sungwon
Ryu, Ji-Hwan
Lee, Jin Hwa
Park, Moo Suk
Kim, Young Sam
Moon, Jong-Seok
author_sort Lee, Su Hwan
collection PubMed
description Dysfunction of mitochondrial metabolism is implicated in cellular injury and cell death. While mitochondrial dysfunction is associated with lung injury by lung inflammation, the mechanism by which the impairment of mitochondrial ATP synthesis regulates necroptosis during acute lung injury (ALI) by lung inflammation is unclear. Here, we showed that the impairment of mitochondrial ATP synthesis induces receptor interacting serine/threonine kinase 3 (RIPK3)-dependent necroptosis during lung injury by lung inflammation. We found that the impairment of mitochondrial ATP synthesis by oligomycin, an inhibitor of ATP synthase, resulted in increased lung injury and RIPK3 levels in lung tissues during lung inflammation by LPS in mice. The elevated RIPK3 and RIPK3 phosphorylation levels by oligomycin resulted in high mixed lineage kinase domain-like (MLKL) phosphorylation, the terminal molecule in necroptotic cell death pathway, in lung epithelial cells during lung inflammation. Moreover, the levels of protein in bronchoalveolar lavage fluid (BALF) were increased by the activation of necroptosis via oligomycin during lung inflammation. Furthermore, the levels of ATP5A, a catalytic subunit of the mitochondrial ATP synthase complex for ATP synthesis, were reduced in lung epithelial cells of lung tissues from patients with acute respiratory distress syndrome (ARDS), the most severe form of ALI. The levels of RIPK3, RIPK3 phosphorylation and MLKL phosphorylation were elevated in lung epithelial cells in patients with ARDS. Our results suggest that the impairment of mitochondrial ATP synthesis induces RIPK3-dependent necroptosis in lung epithelial cells during lung injury by lung inflammation.
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spelling pubmed-90660082022-05-12 Impairment of Mitochondrial ATP Synthesis Induces RIPK3-dependent Necroptosis in Lung Epithelial Cells During Lung Injury by Lung Inflammation Lee, Su Hwan Shin, Ju Hye Park, Min Woo Kim, Junhyung Chung, Kyung Soo Na, Sungwon Ryu, Ji-Hwan Lee, Jin Hwa Park, Moo Suk Kim, Young Sam Moon, Jong-Seok Immune Netw Original Article Dysfunction of mitochondrial metabolism is implicated in cellular injury and cell death. While mitochondrial dysfunction is associated with lung injury by lung inflammation, the mechanism by which the impairment of mitochondrial ATP synthesis regulates necroptosis during acute lung injury (ALI) by lung inflammation is unclear. Here, we showed that the impairment of mitochondrial ATP synthesis induces receptor interacting serine/threonine kinase 3 (RIPK3)-dependent necroptosis during lung injury by lung inflammation. We found that the impairment of mitochondrial ATP synthesis by oligomycin, an inhibitor of ATP synthase, resulted in increased lung injury and RIPK3 levels in lung tissues during lung inflammation by LPS in mice. The elevated RIPK3 and RIPK3 phosphorylation levels by oligomycin resulted in high mixed lineage kinase domain-like (MLKL) phosphorylation, the terminal molecule in necroptotic cell death pathway, in lung epithelial cells during lung inflammation. Moreover, the levels of protein in bronchoalveolar lavage fluid (BALF) were increased by the activation of necroptosis via oligomycin during lung inflammation. Furthermore, the levels of ATP5A, a catalytic subunit of the mitochondrial ATP synthase complex for ATP synthesis, were reduced in lung epithelial cells of lung tissues from patients with acute respiratory distress syndrome (ARDS), the most severe form of ALI. The levels of RIPK3, RIPK3 phosphorylation and MLKL phosphorylation were elevated in lung epithelial cells in patients with ARDS. Our results suggest that the impairment of mitochondrial ATP synthesis induces RIPK3-dependent necroptosis in lung epithelial cells during lung injury by lung inflammation. The Korean Association of Immunologists 2022-04-15 /pmc/articles/PMC9066008/ /pubmed/35573150 http://dx.doi.org/10.4110/in.2022.22.e18 Text en Copyright © 2022. The Korean Association of Immunologists https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Lee, Su Hwan
Shin, Ju Hye
Park, Min Woo
Kim, Junhyung
Chung, Kyung Soo
Na, Sungwon
Ryu, Ji-Hwan
Lee, Jin Hwa
Park, Moo Suk
Kim, Young Sam
Moon, Jong-Seok
Impairment of Mitochondrial ATP Synthesis Induces RIPK3-dependent Necroptosis in Lung Epithelial Cells During Lung Injury by Lung Inflammation
title Impairment of Mitochondrial ATP Synthesis Induces RIPK3-dependent Necroptosis in Lung Epithelial Cells During Lung Injury by Lung Inflammation
title_full Impairment of Mitochondrial ATP Synthesis Induces RIPK3-dependent Necroptosis in Lung Epithelial Cells During Lung Injury by Lung Inflammation
title_fullStr Impairment of Mitochondrial ATP Synthesis Induces RIPK3-dependent Necroptosis in Lung Epithelial Cells During Lung Injury by Lung Inflammation
title_full_unstemmed Impairment of Mitochondrial ATP Synthesis Induces RIPK3-dependent Necroptosis in Lung Epithelial Cells During Lung Injury by Lung Inflammation
title_short Impairment of Mitochondrial ATP Synthesis Induces RIPK3-dependent Necroptosis in Lung Epithelial Cells During Lung Injury by Lung Inflammation
title_sort impairment of mitochondrial atp synthesis induces ripk3-dependent necroptosis in lung epithelial cells during lung injury by lung inflammation
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9066008/
https://www.ncbi.nlm.nih.gov/pubmed/35573150
http://dx.doi.org/10.4110/in.2022.22.e18
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