Molecular Mechanisms of mtDNA-Mediated Inflammation

Besides their role in cell metabolism, mitochondria display many other functions. Mitochondrial DNA (mtDNA), the own genome of the organelle, plays an important role in modulating the inflammatory immune response. When released from the mitochondrion to the cytosol, mtDNA is recognized by cGAS, a cG...

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Autores principales:	Anna De Gaetano, Kateryna Solodka, Giada Zanini, Valentina Selleri, Anna Vittoria Mattioli, Milena Nasi, Marcello Pinti
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mtDNA mitochondria extracellular cf-mtDNA STING TLR9 inflammasome Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8051d5b5ce1247289322d7e1526fd3a5
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id	oai:doaj.org-article:8051d5b5ce1247289322d7e1526fd3a5
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spelling	oai:doaj.org-article:8051d5b5ce1247289322d7e1526fd3a52021-11-25T17:08:41ZMolecular Mechanisms of mtDNA-Mediated Inflammation10.3390/cells101128982073-4409https://doaj.org/article/8051d5b5ce1247289322d7e1526fd3a52021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2898https://doaj.org/toc/2073-4409Besides their role in cell metabolism, mitochondria display many other functions. Mitochondrial DNA (mtDNA), the own genome of the organelle, plays an important role in modulating the inflammatory immune response. When released from the mitochondrion to the cytosol, mtDNA is recognized by cGAS, a cGAMP which activates a pathway leading to enhanced expression of type I interferons, and by NLRP3 inflammasome, which promotes the activation of pro-inflammatory cytokines Interleukin-1beta and Interleukin-18. Furthermore, mtDNA can be bound by Toll-like receptor 9 in the endosome and activate a pathway that ultimately leads to the expression of pro-inflammatory cytokines. mtDNA is released in the extracellular space in different forms (free DNA, protein-bound DNA fragments) either as free circulating molecules or encapsulated in extracellular vesicles. In this review, we discussed the latest findings concerning the molecular mechanisms that regulate the release of mtDNA from mitochondria, and the mechanisms that connect mtDNA misplacement to the activation of inflammation in different pathophysiological conditions.Anna De GaetanoKateryna SolodkaGiada ZaniniValentina SelleriAnna Vittoria MattioliMilena NasiMarcello PintiMDPI AGarticlemtDNAmitochondriaextracellular cf-mtDNASTINGTLR9inflammasomeBiology (General)QH301-705.5ENCells, Vol 10, Iss 2898, p 2898 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mtDNA mitochondria extracellular cf-mtDNA STING TLR9 inflammasome Biology (General) QH301-705.5
spellingShingle	mtDNA mitochondria extracellular cf-mtDNA STING TLR9 inflammasome Biology (General) QH301-705.5 Anna De Gaetano Kateryna Solodka Giada Zanini Valentina Selleri Anna Vittoria Mattioli Milena Nasi Marcello Pinti Molecular Mechanisms of mtDNA-Mediated Inflammation
description	Besides their role in cell metabolism, mitochondria display many other functions. Mitochondrial DNA (mtDNA), the own genome of the organelle, plays an important role in modulating the inflammatory immune response. When released from the mitochondrion to the cytosol, mtDNA is recognized by cGAS, a cGAMP which activates a pathway leading to enhanced expression of type I interferons, and by NLRP3 inflammasome, which promotes the activation of pro-inflammatory cytokines Interleukin-1beta and Interleukin-18. Furthermore, mtDNA can be bound by Toll-like receptor 9 in the endosome and activate a pathway that ultimately leads to the expression of pro-inflammatory cytokines. mtDNA is released in the extracellular space in different forms (free DNA, protein-bound DNA fragments) either as free circulating molecules or encapsulated in extracellular vesicles. In this review, we discussed the latest findings concerning the molecular mechanisms that regulate the release of mtDNA from mitochondria, and the mechanisms that connect mtDNA misplacement to the activation of inflammation in different pathophysiological conditions.
format	article
author	Anna De Gaetano Kateryna Solodka Giada Zanini Valentina Selleri Anna Vittoria Mattioli Milena Nasi Marcello Pinti
author_facet	Anna De Gaetano Kateryna Solodka Giada Zanini Valentina Selleri Anna Vittoria Mattioli Milena Nasi Marcello Pinti
author_sort	Anna De Gaetano
title	Molecular Mechanisms of mtDNA-Mediated Inflammation
title_short	Molecular Mechanisms of mtDNA-Mediated Inflammation
title_full	Molecular Mechanisms of mtDNA-Mediated Inflammation
title_fullStr	Molecular Mechanisms of mtDNA-Mediated Inflammation
title_full_unstemmed	Molecular Mechanisms of mtDNA-Mediated Inflammation
title_sort	molecular mechanisms of mtdna-mediated inflammation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8051d5b5ce1247289322d7e1526fd3a5
work_keys_str_mv	AT annadegaetano molecularmechanismsofmtdnamediatedinflammation AT katerynasolodka molecularmechanismsofmtdnamediatedinflammation AT giadazanini molecularmechanismsofmtdnamediatedinflammation AT valentinaselleri molecularmechanismsofmtdnamediatedinflammation AT annavittoriamattioli molecularmechanismsofmtdnamediatedinflammation AT milenanasi molecularmechanismsofmtdnamediatedinflammation AT marcellopinti molecularmechanismsofmtdnamediatedinflammation
_version_	1718412658832572416

Molecular Mechanisms of mtDNA-Mediated Inflammation

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