ArticleFree radical biology & medicine2012
In vitro oxidative inactivation of human presequence protease (hPreP).
Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Disturb mitochondrial associated proteostasis: Neurodegeneration and imperfect ageing.Frontiers in cell and developmental biology · 2023Review
- Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer's disease-like pathology in human cerebral organoids.Molecular psychiatry · 2021Article
- Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis.International journal of molecular sciences · 2021Review
- Molecular Targets in Alzheimer's Disease.Molecular neurobiology · 2019Review
- An Exome-Wide Association Study Identifies New Susceptibility Loci for Age of Smoking Initiation in African- and European-American Populations.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019Article
- Functional requirement for human pitrilysin metallopeptidase 1 arginine 183, mutated in amyloidogenic neuropathy.Protein science : a publication of the Protein Society · 2018Article
- Defective PITRM1 mitochondrial peptidase is associated with Aβ amyloidotic neurodegeneration.EMBO molecular medicine · 2016Article
- Perturbation of cellular proteostasis networks identifies pathways that modulate precursor and intermediate but not mature levels of frataxin.Scientific reports · 2015Article
- Mechanism of oxidative inactivation of human presequence protease by hydrogen peroxide.Free radical biology & medicine · 2014Article
- Identification of human presequence protease (hPreP) agonists for the treatment of Alzheimer's disease.European journal of medicinal chemistry · 2014Article
- Mitochondrial dysfunction: different routes to Alzheimer's disease therapy.Oxidative medicine and cellular longevity · 2014Review
- Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The mitochondrial peptidasome called presequence protease (PreP) is responsible for the degradation of presequences and other unstructured peptides including the amyloid-β 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 (H(2)O(2)), on the activity of recombinant human PreP (hPreP). H(2)O(2) 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 M206 as internal antioxidant. The activity of hPreP oxidized at low concentrations of H(2)O(2) 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.