Hormesis enables cells to handle accumulating toxic metabolites during increased energy flux
Energy production is inevitably linked to the generation of toxic metabolites, such as reactive oxygen and carbonyl species, known as major contributors to ageing and degenerative diseases. It remains unclear how cells can adapt to elevated energy flux accompanied by accumulating harmful by-products...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
12 August 2017
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| In: |
Redox Biology
Year: 2017, Volume: 13, Pages: 674-686 |
| ISSN: | 2213-2317 |
| DOI: | 10.1016/j.redox.2017.08.007 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1016/j.redox.2017.08.007 Verlag, kostenfrei, Volltext: http://www.sciencedirect.com/science/article/pii/S2213231717305165 
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| Author Notes: | Johanna Zemva, Christoph Andreas Fink, Thomas Henry Fleming, Leonard Schmidt, Anne Loft, Stephan Herzig, Robert André Knieß, Matthias Mayer, Bernd Bukau, Peter Paul Nawroth, Jens Tyedmers |
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| 520 | |a Energy production is inevitably linked to the generation of toxic metabolites, such as reactive oxygen and carbonyl species, known as major contributors to ageing and degenerative diseases. It remains unclear how cells can adapt to elevated energy flux accompanied by accumulating harmful by-products without taking any damage. Therefore, effects of a sudden rise in glucose concentrations were studied in yeast cells. This revealed a feedback mechanism initiated by the reactive dicarbonyl methylglyoxal, which is formed non-enzymatically during glycolysis. Low levels of methylglyoxal activate a multi-layered defence response against toxic metabolites composed of prevention, detoxification and damage remission. The latter is mediated by the protein quality control system and requires inducible Hsp70 and Btn2, the aggregase that sequesters misfolded proteins. This glycohormetic mechanism enables cells to pre-adapt to rising energy flux and directly links metabolic to proteotoxic stress. Further data suggest the existence of a similar response in endothelial cells. | ||
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| 650 | 4 | |a Methylglyoxal | |
| 650 | 4 | |a Nutrient signalling | |
| 650 | 4 | |a Protein quality control system | |
| 650 | 4 | |a Reactive metabolites | |
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