The mammalian peroxisomal membrane is permeable to both GSH and GSSG - Implications for intraperoxisomal redox homeostasis.

Autor:	Ferreira MJ; Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal., Rodrigues TA; Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal., Pedrosa AG; Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal., Gales L; Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal., Salvador A; Coimbra Chemistry Center-Institute of Molecular Sciences (CQC-IMS), University of Coimbra, 3004-535, Coimbra, Portugal; CNC-Center for Neuroscience and Cell Biology, 3004-504, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, 3030-789, Coimbra, Portugal., Francisco T; Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. Electronic address: taniaf@ibmc.up.pt., Azevedo JE; Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. Electronic address: jazevedo@ibmc.up.pt.
Jazyk:	angličtina
Zdroj:	Redox biology [Redox Biol] 2023 Jul; Vol. 63, pp. 102764. Date of Electronic Publication: 2023 May 25.
DOI:	10.1016/j.redox.2023.102764
Abstrakt:	Despite the large amounts of H 2 O 2 generated in mammalian peroxisomes, cysteine residues of intraperoxisomal proteins are maintained in a reduced state. The biochemistry behind this phenomenon remains unexplored, and simple questions such as "is the peroxisomal membrane permeable to glutathione?" or "is there a thiol-disulfide oxidoreductase in the organelle matrix?" still have no answer. We used a cell-free in vitro system to equip rat liver peroxisomes with a glutathione redox sensor. The organelles were then incubated with glutathione solutions of different redox potentials and the oxidation/reduction kinetics of the redox sensor was monitored. The data suggest that the mammalian peroxisomal membrane is promptly permeable to both reduced and oxidized glutathione. No evidence for the presence of a robust thiol-disulfide oxidoreductase in the peroxisomal matrix could be found. Also, prolonged incubation of organelle suspensions with glutaredoxin 1 did not result in the internalization of the enzyme. To explore a potential role of glutathione in intraperoxisomal redox homeostasis we performed kinetic simulations. The results suggest that even in the absence of a glutaredoxin, glutathione is more important in protecting cysteine residues of matrix proteins from oxidation by H 2 O 2 than peroxisomal catalase itself. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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