Peroxiredoxins Play an Important Role in the Regulation of Immunity and Aging in <em>Drosophila</em>

Aberrant immune responses and chronic inflammation can impose significant health risks and promote premature aging. Pro-inflammatory responses are largely mediated via reactive oxygen species (ROS) and reduction–oxidation reactions. A pivotal role in maintaining cellular redox homeostasis and the pr...

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Main Authors: Olena Odnokoz, Noah Earland, Marziyeh Badinloo, Vladimir I. Klichko, Judith Benes, William C. Orr, Svetlana N. Radyuk
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/12/8/1616
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author Olena Odnokoz
Noah Earland
Marziyeh Badinloo
Vladimir I. Klichko
Judith Benes
William C. Orr
Svetlana N. Radyuk
author_facet Olena Odnokoz
Noah Earland
Marziyeh Badinloo
Vladimir I. Klichko
Judith Benes
William C. Orr
Svetlana N. Radyuk
author_sort Olena Odnokoz
collection DOAJ
description Aberrant immune responses and chronic inflammation can impose significant health risks and promote premature aging. Pro-inflammatory responses are largely mediated via reactive oxygen species (ROS) and reduction–oxidation reactions. A pivotal role in maintaining cellular redox homeostasis and the proper control of redox-sensitive signaling belongs to a family of antioxidant and redox-regulating thiol-related peroxidases designated as peroxiredoxins (Prx). Our recent studies in <i>Drosophila</i> have shown that Prxs play a critical role in aging and immunity. We identified two important ‘hubs’, the endoplasmic reticulum (ER) and mitochondria, where extracellular and intracellular stress signals are transformed into pro-inflammatory responses that are modulated by the activity of the Prxs residing in these cellular organelles. Here, we found that mitochondrial Prx activity in the intestinal epithelium is required to prevent the development of intestinal barrier dysfunction, which can drive systemic inflammation and premature aging. Using a redox-negative mutant, we demonstrated that Prx acts in a redox-dependent manner in regulating the age-related immune response. The hyperactive immune response observed in flies under-expressing mitochondrial Prxs is due to a response to abiotic signals but not to changes in the bacterial content. This hyperactive response, but not reduced lifespan phenotype, can be rescued by the ER-localized Prx.
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spelling doaj.art-7cc206844c5941a6864bf3fbd409909f2023-11-19T00:02:47ZengMDPI AGAntioxidants2076-39212023-08-01128161610.3390/antiox12081616Peroxiredoxins Play an Important Role in the Regulation of Immunity and Aging in <em>Drosophila</em>Olena Odnokoz0Noah Earland1Marziyeh Badinloo2Vladimir I. Klichko3Judith Benes4William C. Orr5Svetlana N. Radyuk6Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USADepartment of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USADepartment of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USADepartment of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USADepartment of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USADepartment of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USADepartment of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USAAberrant immune responses and chronic inflammation can impose significant health risks and promote premature aging. Pro-inflammatory responses are largely mediated via reactive oxygen species (ROS) and reduction–oxidation reactions. A pivotal role in maintaining cellular redox homeostasis and the proper control of redox-sensitive signaling belongs to a family of antioxidant and redox-regulating thiol-related peroxidases designated as peroxiredoxins (Prx). Our recent studies in <i>Drosophila</i> have shown that Prxs play a critical role in aging and immunity. We identified two important ‘hubs’, the endoplasmic reticulum (ER) and mitochondria, where extracellular and intracellular stress signals are transformed into pro-inflammatory responses that are modulated by the activity of the Prxs residing in these cellular organelles. Here, we found that mitochondrial Prx activity in the intestinal epithelium is required to prevent the development of intestinal barrier dysfunction, which can drive systemic inflammation and premature aging. Using a redox-negative mutant, we demonstrated that Prx acts in a redox-dependent manner in regulating the age-related immune response. The hyperactive immune response observed in flies under-expressing mitochondrial Prxs is due to a response to abiotic signals but not to changes in the bacterial content. This hyperactive response, but not reduced lifespan phenotype, can be rescued by the ER-localized Prx.https://www.mdpi.com/2076-3921/12/8/1616peroxiredoxinreactive oxygen speciesredox stateimmunityagingmitochondria
spellingShingle Olena Odnokoz
Noah Earland
Marziyeh Badinloo
Vladimir I. Klichko
Judith Benes
William C. Orr
Svetlana N. Radyuk
Peroxiredoxins Play an Important Role in the Regulation of Immunity and Aging in <em>Drosophila</em>
Antioxidants
peroxiredoxin
reactive oxygen species
redox state
immunity
aging
mitochondria
title Peroxiredoxins Play an Important Role in the Regulation of Immunity and Aging in <em>Drosophila</em>
title_full Peroxiredoxins Play an Important Role in the Regulation of Immunity and Aging in <em>Drosophila</em>
title_fullStr Peroxiredoxins Play an Important Role in the Regulation of Immunity and Aging in <em>Drosophila</em>
title_full_unstemmed Peroxiredoxins Play an Important Role in the Regulation of Immunity and Aging in <em>Drosophila</em>
title_short Peroxiredoxins Play an Important Role in the Regulation of Immunity and Aging in <em>Drosophila</em>
title_sort peroxiredoxins play an important role in the regulation of immunity and aging in em drosophila em
topic peroxiredoxin
reactive oxygen species
redox state
immunity
aging
mitochondria
url https://www.mdpi.com/2076-3921/12/8/1616
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