Global Protein Oxidation Profiling Suggests Efficient Mitochondrial Proteome Homeostasis During Aging
| Autor: | Oliver Philipp, Ansgar Poetsch, Sascha Rexroth, Carina Ramallo Guevara, Andrea Hamann, Alexandra Werner, Heinz D. Osiewacz, Matthias Rögner |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Proteomics
0301 basic medicine Oxidative phosphorylation Protein oxidation medicine.disease_cause Biochemistry Podospora anserina Analytical Chemistry Respiratory electron transport chain Fungal Proteins Mitochondrial Proteins 03 medical and health sciences chemistry.chemical_compound Methionine 0302 clinical medicine Podospora Tandem Mass Spectrometry Gene Expression Regulation Fungal medicine Homeostasis Molecular Biology Free-radical theory of aging chemistry.chemical_classification Reactive oxygen species biology Research biology.organism_classification Cell biology Oxidative Stress 030104 developmental biology chemistry Isotope Labeling Reactive Oxygen Species 030217 neurology & neurosurgery Oxidative stress Chromatography Liquid |
| Zdroj: | Molecular & Cellular Proteomics. 15:1692-1709 |
| ISSN: | 1535-9476 |
| DOI: | 10.1074/mcp.m115.055616 |
| Popis: | The free radical theory of aging is based on the idea that reactive oxygen species (ROS) may lead to the accumulation of age-related protein oxidation. Because themajority of cellular ROS is generated at the respiratory electron transport chain, this study focuses on the mitochondrial proteome of the aging model Podospora anserina as target for ROS-induced damage. To ensure the detection of even low abundant modified peptides, separation by long gradient nLC-ESI-MS/MS and an appropriate statistical workflow for iTRAQ quantification was developed. Artificial protein oxidation was minimized by establishing gel-free sample preparation in the presence of reducing and iron-chelating agents. This first large scale, oxidative modification-centric study for P. anserina allowed the comprehensive quantification of 22 different oxidative amino acid modifications, and notably the quantitative comparison of oxidized and nonoxidized protein species. In total 2341 proteins were quantified. For 746 both protein species (unmodified and oxidatively modified) were detected and the modification sites determined. The data revealed that methionine residues are preferably oxidized. Further prominent identified modifications in decreasing order of occurrence were carbonylation as well as formation of N-formylkynurenine and pyrrolidinone. Interestingly, for the majority of proteins a positive correlation of changes in protein amount and oxidative damage were noticed, and a general decrease in protein amounts at late age. However, it was discovered that few proteins changed in oxidative damage in accordance with former reports. Our data suggest that P. anserina is efficiently capable to counteract ROS-induced protein damage during aging as long as protein de novo synthesis is functioning, ultimately leading to an overall constant relationship between damaged and undamaged protein species. These findings contradict a massive increase in protein oxidation during aging and rather suggest a protein damage homeostasis mechanism even at late age. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|