Function of the peroxisomal form of mammalian peroxiredoxin-5
(2014)
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FunctionoftheperoxisomalformofmammalianPRDX5-GeoffroyWalbrecq.pdf
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- Authors
- Supervisors
- Knoops, Bernard
- Abstract
- Peroxisomes are ubiquitous and oxidative organelles which undertake essential reactions in lipid metabolism. The role of peroxisomes is emphasized in various neurodegenerative diseases in which oxidative stress is thought to contribute. PRDX5 is a thiol-specific peroxidase which is found in mitochondria, cytosol and nucleus. In addition, PRDX5 can be targeted to peroxisomes with the use of an unconventional peroxisomal targeting sequence 1 (PTS1). Here, we investigated the function of the mammalian PRDX5 in peroxisomes (po-PRDX5) in murine oligodendrocyte 158N cells. To measure the redox status in peroxisomes, we first evaluated the response of two peroxisomal reduction-oxidation sensitive green fluorescent protein (roGFP) probes, po-roGFP2 and po-Grx1-roGFP2. Po-Grx1-roGFP2 was shown to have a faster and enhanced response to acute oxidative stress compared to po-roGFP2.Moreover, in order to study the function of the po-PRDX5, we selected 158N clones with various localized expression of PRDX5. The cytoprotective function of po-PRDX5 against H2O2 as well as Reactive Oxygen Species (ROS) produced by peroxisomal (po-) and mitochondrial (mt-) localized variants of the photosensitizer KillerRed (KR) was examined using MTT viability assays. Altogether our results show that po-PRDX5 protects 158N oligodendrocytes against po-KR and mt-KR-mediated oxidative stress and against externally added H2O2. Finally, we evaluated the effect of the po- and mt-KR-induced ROS on overoxidation of the PRDX3 and the PRDX5. Our results show that po- and mt-KR-induced ROS can induce a localized overoxidation of PRDX3 and PRDX5. In conclusion, our results demonstrate a cytoprotective role for the mammalian peroxisomal PRDX5 and also shows the usefulness of genetic tools such as roGFP2 and KR to respectively measure and trigger ROS in subcellular compartments.
- Affiliations
Citations
Walbrecq, G. (2014). Function of the peroxisomal form of mammalian peroxiredoxin-5. https://hdl.handle.net/2078.5/199355