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In vitro oxidative inactivation of human presequence protease (hPreP)
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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2012 (English)In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 53, no 11, 2188-2195 p.Article in journal (Refereed) Published
Abstract [en]

The mitochondrial peptidasome called presequence protease (Prep) is responsible for the degradation of presequences and other unstructured peptides including the amyloid-beta, peptide, whose accumulation may have deleterious effects on mitochondrial function. Recent studies showed that PreP activity is reduced in Alzheimer disease (AD) patients and AD mouse models compared to controls, which correlated with an enhanced reactive oxygen species production in mitochondria. In this study, we have investigated the effects of a biologically relevant oxidant, hydrogen peroxide (H2O2), on the activity of recombinant human PreP (hPreP). H2O2 inhibited hPreP activity in a concentration-dependent manner, resulting in oxidation of amino acid residues (detected by carbonylation) and lowered protein stability. Substitution of the evolutionarily conserved methionine 206 for leucine resulted in increased sensitivity of hPreP to oxidation, indicating a possible protective role of M2O6 as internal antioxidant. The activity of hPreP oxidized at low concentrations of H2O2 could be restored by methionine sulfoxide reductase A (MsrA), an enzyme that localizes to the mitochondrial matrix, suggesting that hPreP constitutes a substrate for MsrA. In summary, our in vitro results suggest a possible redox control of hPreP in the mitochondrial matrix and support the protective role of the conserved methionine 206 residue as an internal antioxidant.

Place, publisher, year, edition, pages
2012. Vol. 53, no 11, 2188-2195 p.
Keyword [en]
Mitochondria, Presequence protease, Peptide degradation, Oxidation, Methionine, Free radicals
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-85532DOI: 10.1016/j.freeradbiomed.2012.09.039ISI: 000312058300020OAI: oai:DiVA.org:su-85532DiVA: diva2:585964
Note

AuthorCount:6;

Available from: 2013-01-10 Created: 2013-01-08 Last updated: 2017-12-06Bibliographically approved

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Teixeira, Pedro FilipePinho, Catarina MoreiraGlaser, Elzbieta
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