Mitochondrial peroxiredoxins are essential in regulating the relationship between Drosophila immunity and aging

Mitochondrial peroxiredoxins are essential in regulating the relationship between Drosophila immunity and aging

Previously, we have shown that flies under-expressing the two mitochondrial peroxiredoxins (Prxs), dPrx3 and dPrx5, display increases in tissue-specific apoptosis and dramatically shortened life span, associated with a redox crisis, manifested as changes in GSH:GSSG and accumulation of protein mixed...

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Published in:Biochimica et biophysica acta. Molecular basis of disease Vol. 1863; no. 1; pp. 68 - 80
Main Authors: Odnokoz, Olena, Nakatsuka, Kyle, Klichko, Vladimir I., Nguyen, Jacqueline, Solis, Liz Calderon, Ostling, Kaitlin, Badinloo, Marziyeh, Orr, William C., Radyuk, Svetlana N.
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01-01-2017
Subjects:
Aging
Animals
Drosophila
Drosophila - genetics
Drosophila - immunology
Drosophila - physiology
Drosophila Proteins - genetics
Drosophila Proteins - immunology
Female
Immunity
Male
Mitochondria
Mitochondria - genetics
Mitochondria - immunology
Mitochondrial Proteins - genetics
Mitochondrial Proteins - immunology
Peroxiredoxin
Peroxiredoxins - genetics
Peroxiredoxins - immunology
Redox
Transcriptome
Peroxiredoxin
PQ
AMP
Hsp
Drosophila
Redox
DM
ER
Immunity
BP
PGRP
Mitochondria
NLS
Nucl
Prx
ROS
Aging
Mit
Cyp
Da
Cyt
IRG
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Summary:Previously, we have shown that flies under-expressing the two mitochondrial peroxiredoxins (Prxs), dPrx3 and dPrx5, display increases in tissue-specific apoptosis and dramatically shortened life span, associated with a redox crisis, manifested as changes in GSH:GSSG and accumulation of protein mixed disulfides. To identify specific pathways responsible for the observed biological effects, we performed a transcriptome analysis. Functional clustering revealed a prominent group enriched for immunity-related genes, including a considerable number of NF-kB-dependent antimicrobial peptides (AMP) that are up-regulated in the Prx double mutant. Using qRT-PCR analysis we determined that the age-dependent changes in AMP levels in mutant flies were similar to those observed in controls when scaled to percentage of life span. To further clarify the role of Prx-dependent mitochondrial signaling, we expressed different forms of dPrx5, which unlike the uniquely mitochondrial dPrx3 is found in multiple subcellular compartments, including mitochondrion, nucleus and cytosol. Ectopic expression of dPrx5 in mitochondria but not nucleus or cytosol partially extended longevity under normal or oxidative stress conditions while complete restoration of life span occurred when all three forms of dPrx5 were expressed from the wild type dPrx5 transgene. When dPrx5 was expressed in mitochondria or in all three compartments, it substantially delayed the development of hyperactive immunity while expression of cytosolic or nuclear forms had no effect on the immune phenotype. The data suggest a critical role of mitochondria in development of chronic activation of the immune response triggered by impaired redox control. •Underexpression of mitochondrial peroxiredoxins induces the immune response.•Mitochondrial peroxiredoxin 5 delays the onset of hyperactive immunity.•Mitochondrial peroxiredoxin 5 partially protects from oxidative stress.•Shortened longevity of the double dprx3&5 mutant is rescued by mitochondrial dPrx5.
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content type line 23
ISSN:0925-4439
1879-260X
DOI:10.1016/j.bbadis.2016.10.017