Your browser doesn't support javascript.
loading
Peroxisomes as Modulators of Cellular Protein Thiol Oxidation: A New Model System.
Lismont, Celien; Nordgren, Marcus; Brees, Chantal; Knoops, Bernard; Van Veldhoven, Paul P; Fransen, Marc.
Afiliação
  • Lismont C; 1 Laboratory of Lipid Biochemistry and Protein Interactions, Department of Cellular and Molecular Medicine, KU Leuven-University of Leuven , Leuven, Belgium .
  • Nordgren M; 1 Laboratory of Lipid Biochemistry and Protein Interactions, Department of Cellular and Molecular Medicine, KU Leuven-University of Leuven , Leuven, Belgium .
  • Brees C; 1 Laboratory of Lipid Biochemistry and Protein Interactions, Department of Cellular and Molecular Medicine, KU Leuven-University of Leuven , Leuven, Belgium .
  • Knoops B; 2 Group of Animal Molecular and Cellular Biology, Institut des Sciences de la Vie (ISV), Université catholique de Louvain , Louvain-la-Neuve, Belgium .
  • Van Veldhoven PP; 1 Laboratory of Lipid Biochemistry and Protein Interactions, Department of Cellular and Molecular Medicine, KU Leuven-University of Leuven , Leuven, Belgium .
  • Fransen M; 1 Laboratory of Lipid Biochemistry and Protein Interactions, Department of Cellular and Molecular Medicine, KU Leuven-University of Leuven , Leuven, Belgium .
Antioxid Redox Signal ; 30(1): 22-39, 2019 01 01.
Article em En | MEDLINE | ID: mdl-28594286
ABSTRACT

AIMS:

Peroxisomes are ubiquitous, single-membrane-bounded organelles that contain considerable amounts of enzymes involved in the production or breakdown of hydrogen peroxide (H2O2), a key signaling molecule in multiple biological processes and disease states. Despite this, the role of this organelle in cross-compartmental H2O2 signaling remains largely unclear, mainly because of the difficulty to modulate peroxisomal H2O2 production in a selective manner. This study aimed at establishing and validating a cellular model suitable to decipher the complex signaling processes associated with peroxisomal H2O2 release.

RESULTS:

Here, we report the development of a human cell line that can be used to selectively generate H2O2 inside peroxisomes in a time- and dose-controlled manner. In addition, we provide evidence that peroxisome-derived H2O2 can oxidize redox-sensitive cysteine residues in multiple proteins within (e.g., peroxiredoxin-5 [PRDX5]) and outside (e.g., nuclear factor kappa B subunit 1 [NFKB1] and subunit RELA proto-oncogene [RELA], phosphatase and tensin homolog [PTEN], forkhead box O3 [FOXO3], and peroxin 5 [PEX5]) the peroxisomal compartment. Furthermore, we show that the extent of protein oxidation depends on the subcellular location of the target protein and is inversely correlated to catalase activity and cellular glutathione content. Finally, we demonstrate that excessive H2O2 production inside peroxisomes does not induce their selective degradation, at least not under the conditions examined. INNOVATION This study describes for the first time a powerful model system that can be used to examine the role of peroxisome-derived H2O2 in redox-regulated (patho)physiological processes, a research area in need of further investigation and innovative approaches.

CONCLUSION:

Our results provide unambiguous evidence that peroxisomes can serve as regulatory hubs in thiol-based signaling networks.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Compostos de Sulfidrila / Peroxissomos / Modelos Biológicos Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Compostos de Sulfidrila / Peroxissomos / Modelos Biológicos Idioma: En Ano de publicação: 2019 Tipo de documento: Article