Differential proteomic profiling of mitochondria from Podospora anserina, rat and human reveals distinct patterns of age-related oxidative changes.
According to the 'free radical theory of ageing', the generation and accumulation of reactive oxygen species are key events during ageing of biological systems. Mitochondria are a major source of ROS and prominent targets for ROS-induced damage. Whereas mitochondrial DNA and membranes were shown to be oxidatively modified with ageing, mitochondrial protein oxidation is not well understood. The purpose of this study was an unbiased investigation of age-related changes in mitochondrial proteins and the molecular pathways by which ROS-induced protein oxidation may disturb cellular homeostasis. In a differential comparison of mitochondrial proteins from young and senescent strains of the fungal ageing model Podospora anserina, from brains of young (5 months) vs. older rats (17 and 31 months), and human cells, with normal and chemically accelerated in vitro ageing, we found certain redundant posttranslationally modified isoforms of subunits of ATP synthase affected across all three species. These appear to represent general susceptible hot spot targets for oxidative chemical changes of proteins accumulating during ageing, and potentially initiating various age-related pathologies and processes. This type of modification is discussed using the example of SAM-dependent O-methyltransferase from P. anserina (PaMTH1), which surprisingly was found to be enriched in mitochondrial preparations of senescent cultures.
Groebe
Karlfried
K
ProteoSys AG, Carl Zeiss Strasse 51, 55129 Mainz, Germany.
Krause
Frank
F
Kunstmann
Birgit
B
Unterluggauer
Hermann
H
Reifschneider
Nicole H
NH
Scheckhuber
Christian Q
CQ
Sastri
Charturvedala
C
Stegmann
Werner
W
Wozny
Wojciech
W
Schwall
Gerhard P
GP
Poznanović
Slobodan
S
Dencher
Norbert A
NA
Jansen-Dürr
Pidder
P
Osiewacz
Heinz D
HD
Schrattenholz
André
A
D000375:Aging / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D015180:Electrophoresis, Gel, Two-Dimensional; D005656:Fungal Proteins / Q000032:analysis; D006801:Humans; D008780:Methyltransferases / Q000032:analysis; D008928:Mitochondria / Q000737:chemistry*; D025261:Mitochondrial Proton-Translocating ATPases / Q000032:analysis*; D008954:Models, Biological; D018384:Oxidative Stress; D048468:Podospora / Q000502:physiology; D020033:Protein Isoforms / Q000032:analysis*; D011499:Protein Processing, Post-Translational; D020543:Proteome; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D005656:Fungal Proteins; D020033:Protein Isoforms; D020543:Proteome; D017382:Reactive Oxygen Species; D008780:Methyltransferases; C409687:PaMTH1 protein, Podospora anserina; D025261:Mitochondrial Proton-Translocating ATPases