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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doaj-8aeca16a48664371be95eb4093fd15d02020-11-25T02:45:42ZengElsevierRedox Biology2213-23172017-10-0113C67468610.1016/j.redox.2017.08.007Hormesis enables cells to handle accumulating toxic metabolites during increased energy fluxJohanna Zemva0Christoph Andreas Fink1Thomas Henry Fleming2Leonard Schmidt3Anne Loft4Stephan Herzig5Robert André Knieß6Matthias Mayer7Bernd Bukau8Peter Paul Nawroth9Jens Tyedmers10Department for Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyDepartment for Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyDepartment for Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyDepartment for Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyInstitute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg and Joint Heidelberg-IDC Translational Diabetes Program, Department for Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyInstitute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg and Joint Heidelberg-IDC Translational Diabetes Program, Department for Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyCenter for Molecular Biology of Heidelberg University (ZMBH) and German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, 69120 Heidelberg, GermanyCenter for Molecular Biology of Heidelberg University (ZMBH) and German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, 69120 Heidelberg, GermanyCenter for Molecular Biology of Heidelberg University (ZMBH) and German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, 69120 Heidelberg, GermanyDepartment for Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyDepartment for Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyEnergy 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.http://www.sciencedirect.com/science/article/pii/S2213231717305165MethylglyoxalReactive metabolitesGlucose metabolismNutrient signallingProtein quality control systemHeat shock proteins |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Hormesis enables cells to handle accumulating toxic metabolites during increased energy flux Redox Biology Methylglyoxal Reactive metabolites Glucose metabolism Nutrient signalling Protein quality control system Heat shock proteins |
author_facet |
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 |
author_sort |
Johanna Zemva |
title |
Hormesis enables cells to handle accumulating toxic metabolites during increased energy flux |
title_short |
Hormesis enables cells to handle accumulating toxic metabolites during increased energy flux |
title_full |
Hormesis enables cells to handle accumulating toxic metabolites during increased energy flux |
title_fullStr |
Hormesis enables cells to handle accumulating toxic metabolites during increased energy flux |
title_full_unstemmed |
Hormesis enables cells to handle accumulating toxic metabolites during increased energy flux |
title_sort |
hormesis enables cells to handle accumulating toxic metabolites during increased energy flux |
publisher |
Elsevier |
series |
Redox Biology |
issn |
2213-2317 |
publishDate |
2017-10-01 |
description |
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. |
topic |
Methylglyoxal Reactive metabolites Glucose metabolism Nutrient signalling Protein quality control system Heat shock proteins |
url |
http://www.sciencedirect.com/science/article/pii/S2213231717305165 |
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