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MOLECULAR GENETICS OF LONGEVITY IN ESCHERICHIA COLI
by
Stavros Gonidakis
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(INTEGRATIVE AND EVOLUTIONARY BIOLOGY)
December 2010
Copyright 2010 Stavros Gonidakis
Object Description
| Title | Molecular genetics of longevity in Escherichia coli |
| Author | Gonidakis, Stavros |
| Author email | gonidaki@usc.edu; Stavros@cantab.net |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Integrative & Evolutionary Biology |
| School | College of Letters, Arts and Sciences |
| Date submitted | 2010 |
| Restricted until | Unrestricted |
| Date published | 2010-10-25 |
| Advisor (committee chair) | Longo, Valter D. |
| Advisor (committee member) |
FInkel, Steven E. Petasis, Nicos A. |
| Abstract | Single-gene mutants with extended lifespan have been described in several species. We performed the first genome-wide screen for long-lived mutants in a prokaryotic organism, using the Gram negative bacterium Escherichia coli. The screen revealed strains lacking components of the electron transport chain and the TCA cycle that exhibit longer stationary phase survival and increased resistance to heat and oxidative stress compared to wild-type. Extended survival in the sdhA mutant, lacking subunit A of succinate dehydrogenase, is associated with reduced production of superoxide. On the other hand, the hypoxia-inducible transcription factor ArcA and the bypass of the pyruvate dehydrogenase complex through the pyruvate oxidase / acetyl-CoA synthetase enzyme pair independently contribute to the lenghthened lifespan of the lipoic acid synthase mutant (lipA). Oxidative damage in the formof protein carbonylation does not limit the stationary phase survival of E. coli. Since analogous metabolic changes involving different carbon sources have been observed in long-lived Saccharomyces cerevisiae and Caenorhabditis elegans strains, our results indicate that the switch from respiratory to fermentative metabolism in the presence of oxygen might be an evolutionarily conserved strategy to enhance stress resistance and extend lifespan. |
| Keyword | lifespan; longevity; aging; evolution; Escherichia coli; acetate; hypoxia; bacteria; metabolism; genetics; physiology |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3512 |
| Rights | Gonidakis, Stavros |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Gonidakis-4034 |
| Archival file | uscthesesreloadpub_Volume17/etd-Gonidakis-4034.pdf |
Description
| Title | Page 1 |
| Full text | MOLECULAR GENETICS OF LONGEVITY IN ESCHERICHIA COLI by Stavros Gonidakis A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (INTEGRATIVE AND EVOLUTIONARY BIOLOGY) December 2010 Copyright 2010 Stavros Gonidakis |
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