Por favor, use este identificador para citar o enlazar este ítem: https://hdl.handle.net/20.500.12008/52239

Título:

Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides

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Autor:

Cardozo, Giuliana
Mastrogiovanni, Mauricio
Zeida, Ari
Viera, Nicolás
Radi, Rafael
Reyes, Aníbal M.
Trujillo, Maida

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Tipo de documento:

Artículo

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Palabras clave:

Antioxidant systems
Fatty acid hydroperoxide
Kinetics
Lipid peroxidation
Mitochondria
Peroxiredoxin

Descriptores:

PEROXIRREDOXINAS
PERÓXIDO DE HIDRÓGENO
ÁCIDO PEROXINITROSO
MITOCONDRIAS
PERÓXIDOS LIPÍDICOS
CINÉTICA
PEROXIDACIÓN DE LÍPIDO

Año de publicación:

2023

Contenido:

Resumen:

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.

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MDPI

EN:

Antioxidants. 2023;12(2)

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Citación:

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.

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2076-3921

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Licencia Creative Commons Atribución (CC - By 4.0)

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