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Mitochondrial ageing in rat brain areas and human fibroblasts

Frenzel, Monika (2012):
Mitochondrial ageing in rat brain areas and human fibroblasts.
TU Darmstadt / Chemie, [Online-Edition: urn:nbn:de:tuda-tuprints-29372],
[Ph.D. Thesis]

Abstract

Understanding molecular processes underlying ageing still remains a challenge. Besides genetic determinants and the detrimental effects of reactive oxygen species (ROS), age-dependent changes in the abundance and post-translational modification of the cellular proteome are currently considered as targets and even triggers of ageing. At the protein level, numerous alterations in both the abundance and specific post-translational modification have been previously observed for a variety of established ageing models that might represent control determinants of evolutionary conserved life- and health-span. In this doctoral thesis, the mitochondrial proteome and its alterations during ageing were studied, with a focus specifically on the oxidative phosphorylation machinery. Data obtained from protein profiling of rat brain cortex, striatum and hippocampus of two different age states were compared to that of human fibroblasts undergoing senescence and/or irradiated fibroblasts exposed to X-rays or heavy ions. The focus was on the quantitative analysis of individual Oxidative Phosphorylation (OxPhos) complexes, respiratory chain supercomplexes and ATP synthase oligomers, as well as other non-OxPhos proteins that might be involved in the process of ageing, senescence or radiation response. The most important goal was to determine the overall mechanisms (in vivo and in vitro) in the largely unknown fundamental molecular processes involved in both ageing and senescence.

Item Type: Ph.D. Thesis
Erschienen: 2012
Creators: Frenzel, Monika
Title: Mitochondrial ageing in rat brain areas and human fibroblasts
Language: English
Abstract:

Understanding molecular processes underlying ageing still remains a challenge. Besides genetic determinants and the detrimental effects of reactive oxygen species (ROS), age-dependent changes in the abundance and post-translational modification of the cellular proteome are currently considered as targets and even triggers of ageing. At the protein level, numerous alterations in both the abundance and specific post-translational modification have been previously observed for a variety of established ageing models that might represent control determinants of evolutionary conserved life- and health-span. In this doctoral thesis, the mitochondrial proteome and its alterations during ageing were studied, with a focus specifically on the oxidative phosphorylation machinery. Data obtained from protein profiling of rat brain cortex, striatum and hippocampus of two different age states were compared to that of human fibroblasts undergoing senescence and/or irradiated fibroblasts exposed to X-rays or heavy ions. The focus was on the quantitative analysis of individual Oxidative Phosphorylation (OxPhos) complexes, respiratory chain supercomplexes and ATP synthase oligomers, as well as other non-OxPhos proteins that might be involved in the process of ageing, senescence or radiation response. The most important goal was to determine the overall mechanisms (in vivo and in vitro) in the largely unknown fundamental molecular processes involved in both ageing and senescence.

Divisions: 07 Department of Chemistry > Fachgebiet Biochemie
07 Department of Chemistry
Date Deposited: 13 Apr 2012 11:39
Official URL: urn:nbn:de:tuda-tuprints-29372
License: only the rights of use according to UrhG
Referees: Dencher, Prof. Dr. N. A. and Thiel, Prof. Dr. G. and Durante, Prof. Dr. M.
Refereed / Verteidigung / mdl. Prüfung: 17 May 2011
Alternative Abstract:
Alternative abstract Language
Die molekularen Abläufe des Alternsprozesses zu verstehen, stellt noch immer eine große Herausforderung dar. Neben genetischen Faktoren und der schädlichen Wirkung reaktiver Sauerstoffspezies (ROS), werden alternsabhängige Veränderungen der Proteinmengen und post-translationale Modifikationen des zellulären Proteoms derzeit als Angriffspunkte bei der Alterung bzw. als Ursache des Alterns betrachtet. Bei einer Vielzahl bereits vorhandener Modelle, die das Altern beschreiben, wurden auf Proteinebene zahlreiche quantitative Veränderungen der Proteinmengen sowie ein vermehrtes Auftreten spezifischer post-translationaler Modifikation beobachtet. Dabei handelt es sich möglicherweise um allgemeingültige Faktoren, die die Lebens- und Gesundheitsspanne evolutionär beeinflussen. Ziel dieser Promotionsarbeit war es, das mitochondriale Proteom, insbesondere im Hinblick auf die Oxidative Phosphorylierung (OxPhos), auf seine Veränderungen im Alter hin zu untersuchen. Speziell wurden im ersten Schritt drei verschiedene Areale (Cortex, Striatum und Hippocampus) aus Rattenhirn zweier Altersstufen verglichen. Erhaltene Ergebnisse konnten in einem zweiten Schritt zu Veränderungen des mitochondrialen Proteoms humaner Fibroblasten beim Eintritt in die Seneszenz und nach Bestrahlung mit Röntgenstrahlen bzw. schweren Ionen in Bezug gesetzt werden. Der Schwerpunkt lag dabei stets auf der quantitativen Analyse der Atmungskettenkomplexe und ihrer Superkomplexe, sowie dem Auftreten von ATP-Synthase Oligomeren und Nicht-OxPhos-Proteinen, die möglicherweise am Altern, der Seneszenz oder der zellulären Antwort auf Bestrahlung beteiligt sind. Generelle Mechanismen (in vivo und in vitro), die Aufschluss sowohl über den zurzeit noch weitestgehend unverstandenen Prozess des Alterns sowie der zellulären Seneszenz geben, wurden erforscht.German
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