Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides
Human peroxiredoxin 3 (HsPrx3) is a thiol-based peroxidase responsible for the reduction of most hydrogen peroxide and peroxynitrite formed in mitochondria. Mitochondrial disfunction can lead to membrane lipoperoxidation, resulting in the formation of lipid-bound fatty acid hydroperoxides (LFA-OOHs)...
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| Aineistotyyppi: | article |
| Kieli: | englanti |
| Julkaistu: |
2023
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| Linkit: | https://hdl.handle.net/20.500.12008/52239 |
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| _version_ | 1868889961270345728 |
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| author | Cardozo, Giuliana |
| author2 | Mastrogiovanni, Mauricio Zeida, Ari Viera, Nicolás Radi, Rafael Reyes, Aníbal M. Trujillo, Maida |
| author2_role | author author author author author author |
| author_browse | Cardozo, Giuliana Mastrogiovanni, Mauricio Radi, Rafael Reyes, Aníbal M. Trujillo, Maida Viera, Nicolás Zeida, Ari |
| author_facet | Cardozo, Giuliana Mastrogiovanni, Mauricio Zeida, Ari Viera, Nicolás Radi, Rafael Reyes, Aníbal M. Trujillo, Maida |
| author_role | author |
| collection | COLIBRI |
| dc.contributor.none.fl_str_mv | Cardozo Giuliana, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones Biomédicas Mastrogiovanni Mauricio, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones Biomédicas Zeida Ari, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones Biomédicas Viera Nicolás, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones Biomédicas Radi Rafael, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones Biomédicas Reyes Aníbal M., Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones Biomédicas Trujillo Maida, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones Biomédicas |
| dc.creator.none.fl_str_mv | Cardozo, Giuliana Mastrogiovanni, Mauricio Zeida, Ari Viera, Nicolás Radi, Rafael Reyes, Aníbal M. Trujillo, Maida |
| dc.date.none.fl_str_mv | 2023 2025-10-24T18:10:34Z 2025-10-24T18:10:34Z |
| dc.format.none.fl_str_mv | 22 p. application/pdf |
| dc.identifier.none.fl_str_mv | Cardozo G, Mastrogiovanni M, Zeida A y otros. Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides. Antioxidants [en línea]. 2023;12(2). 22 p. 2076-3921 https://hdl.handle.net/20.500.12008/52239 10.3390/antiox12020408 |
| dc.language.none.fl_str_mv | en eng |
| dc.publisher.none.fl_str_mv | MDPI |
| dc.relation.none.fl_str_mv | Antioxidants. 2023;12(2) |
| dc.rights.none.fl_str_mv | info:eu-repo/semantics/openAccess Licencia Creative Commons Atribución (CC - By 4.0) |
| dc.source.none.fl_str_mv | reponame:COLIBRI instname:Universidad de la República instacron:Universidad de la República |
| dc.subject.none.fl_str_mv | Antioxidant systems Fatty acid hydroperoxide Kinetics Lipid peroxidation Mitochondria Peroxiredoxin PEROXIRREDOXINAS PERÓXIDO DE HIDRÓGENO ÁCIDO PEROXINITROSO MITOCONDRIAS PERÓXIDOS LIPÍDICOS CINÉTICA PEROXIDACIÓN DE LÍPIDO |
| dc.title.none.fl_str_mv | Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides |
| dc.type.none.fl_str_mv | Artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| description | Human peroxiredoxin 3 (HsPrx3) is a thiol-based peroxidase responsible for the reduction of most hydrogen peroxide and peroxynitrite formed in mitochondria. Mitochondrial disfunction can lead to membrane lipoperoxidation, resulting in the formation of lipid-bound fatty acid hydroperoxides (LFA-OOHs) which can be released to become free fatty acid hydroperoxides (fFA-OOHs). Herein, we report that HsPrx3 is oxidized and hyperoxidized by fFA-OOHs including those derived from arachidonic acid and eicosapentaenoic acid peroxidation at position 15 with remarkably high rate constants of oxidation (>3.5 × 107 M-1s-1) and hyperoxidation (~2 × 107 M-1s-1). The endoperoxide-hydroperoxide PGG2, an intermediate in prostanoid synthesis, oxidized HsPrx3 with a similar rate constant, but was less effective in causing hyperoxidation. Biophysical methodologies suggest that HsPrx3 can bind hydrophobic structures. Indeed, molecular dynamic simulations allowed the identification of a hydrophobic patch near the enzyme active site that can allocate the hydroperoxide group of fFA-OOHs in close proximity to the thiolate in the peroxidatic cysteine. Simulations performed using available and herein reported kinetic data indicate that HsPrx3 should be considered a main target for mitochondrial fFA-OOHs. Finally, kinetic simulation analysis support that mitochondrial fFA-OOHs formation fluxes in the range of nM/s are expected to contribute to HsPrx3 hyperoxidation, a modification that has been detected in vivo under physiological and pathological conditions. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | anni_129e1a2b09ab53b7492682dfd5ed6a56 |
| identifier_str_mv | Cardozo G, Mastrogiovanni M, Zeida A y otros. Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides. Antioxidants [en línea]. 2023;12(2). 22 p. 2076-3921 10.3390/antiox12020408 |
| instacron_str | Universidad de la República |
| institution | Universidad de la República |
| instname_str | Universidad de la República |
| language | eng |
| language_invalid_str_mv | en |
| network_acronym_str | anni |
| network_name_str | oai-lr-anni |
| oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/52239 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| publisher.none.fl_str_mv | MDPI |
| reponame_str | COLIBRI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
| spelling | Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid HydroperoxidesCardozo, GiulianaMastrogiovanni, MauricioZeida, AriViera, NicolásRadi, RafaelReyes, Aníbal M.Trujillo, MaidaAntioxidant systemsFatty acid hydroperoxideKineticsLipid peroxidationMitochondriaPeroxiredoxinPEROXIRREDOXINASPERÓXIDO DE HIDRÓGENOÁCIDO PEROXINITROSOMITOCONDRIASPERÓXIDOS LIPÍDICOSCINÉTICAPEROXIDACIÓN DE LÍPIDOHuman peroxiredoxin 3 (HsPrx3) is a thiol-based peroxidase responsible for the reduction of most hydrogen peroxide and peroxynitrite formed in mitochondria. Mitochondrial disfunction can lead to membrane lipoperoxidation, resulting in the formation of lipid-bound fatty acid hydroperoxides (LFA-OOHs) which can be released to become free fatty acid hydroperoxides (fFA-OOHs). Herein, we report that HsPrx3 is oxidized and hyperoxidized by fFA-OOHs including those derived from arachidonic acid and eicosapentaenoic acid peroxidation at position 15 with remarkably high rate constants of oxidation (>3.5 × 107 M-1s-1) and hyperoxidation (~2 × 107 M-1s-1). The endoperoxide-hydroperoxide PGG2, an intermediate in prostanoid synthesis, oxidized HsPrx3 with a similar rate constant, but was less effective in causing hyperoxidation. Biophysical methodologies suggest that HsPrx3 can bind hydrophobic structures. Indeed, molecular dynamic simulations allowed the identification of a hydrophobic patch near the enzyme active site that can allocate the hydroperoxide group of fFA-OOHs in close proximity to the thiolate in the peroxidatic cysteine. Simulations performed using available and herein reported kinetic data indicate that HsPrx3 should be considered a main target for mitochondrial fFA-OOHs. Finally, kinetic simulation analysis support that mitochondrial fFA-OOHs formation fluxes in the range of nM/s are expected to contribute to HsPrx3 hyperoxidation, a modification that has been detected in vivo under physiological and pathological conditions.MDPICardozo Giuliana, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones BiomédicasMastrogiovanni Mauricio, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones BiomédicasZeida Ari, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones BiomédicasViera Nicolás, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones BiomédicasRadi Rafael, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones BiomédicasReyes Aníbal M., Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones BiomédicasTrujillo Maida, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones Biomédicas2025-10-24T18:10:34Z2025-10-24T18:10:34Z2023Artículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion22 p.application/pdfCardozo G, Mastrogiovanni M, Zeida A y otros. Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides. Antioxidants [en línea]. 2023;12(2). 22 p.2076-3921https://hdl.handle.net/20.500.12008/5223910.3390/antiox12020408reponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaenengAntioxidants. 2023;12(2)Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)oai:colibri.udelar.edu.uy:20.500.12008/522392026-04-14T10:28:21Z |
| spellingShingle | Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides Cardozo, Giuliana Antioxidant systems Fatty acid hydroperoxide Kinetics Lipid peroxidation Mitochondria Peroxiredoxin PEROXIRREDOXINAS PERÓXIDO DE HIDRÓGENO ÁCIDO PEROXINITROSO MITOCONDRIAS PERÓXIDOS LIPÍDICOS CINÉTICA PEROXIDACIÓN DE LÍPIDO |
| status_str | publishedVersion |
| title | Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides |
| title_full | Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides |
| title_fullStr | Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides |
| title_full_unstemmed | Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides |
| title_short | Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides |
| title_sort | Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides |
| topic | Antioxidant systems Fatty acid hydroperoxide Kinetics Lipid peroxidation Mitochondria Peroxiredoxin PEROXIRREDOXINAS PERÓXIDO DE HIDRÓGENO ÁCIDO PEROXINITROSO MITOCONDRIAS PERÓXIDOS LIPÍDICOS CINÉTICA PEROXIDACIÓN DE LÍPIDO |
| url | https://hdl.handle.net/20.500.12008/52239 |