Regulation of Lifespan by the Mitochondrial Electron Transport Chain: Reactive Oxygen Species-Dependent and Reactive Oxygen Species-Independent Mechanisms

2013 ◽  
Vol 19 (16) ◽  
pp. 1953-1969 ◽  
Author(s):  
Filippo Scialo ◽  
Venkatesh Mallikarjun ◽  
Rhoda Stefanatos ◽  
Alberto Sanz
Keyword(s):  
Reactive Oxygen Species ◽  
Electron Transport ◽  
Electron Transport Chain ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Mitochondrial Electron Transport Chain ◽  
Transport Chain

scholarly journals Haem oxygenase 1 gene induction by glucose deprivation is mediated by reactive oxygen species via the mitochondrial electron-transport chain

2003 ◽  
Vol 371 (3) ◽  
pp. 877-885 ◽  
Author(s):  
Se-Ho CHANG ◽  
Jairo GARCIA ◽  
J. Andres MELENDEZ ◽  
Michael S. KILBERG ◽  
Anupam AGARWAL
Keyword(s):  
Reactive Oxygen Species ◽  
Electron Transport ◽  
Protein Kinase ◽  
Electron Transport Chain ◽  
Reactive Oxygen ◽  
Glucose Deprivation ◽  
Oxygen Species ◽  
Mitochondrial Electron Transport Chain ◽  
Transport Chain ◽  
Haem Oxygenase

Glucose depletion results in cellular stress and reactive oxygen species (ROS) production, which evokes adaptive and protective responses. One such protective response is the induction of haem oxygenase 1 (HO-1), which catalyses the rate-limiting step in haem degradation, liberating iron, CO and biliverdin. The present study evaluated the role of ROS and the mitochondrial electron-transport chain in the induction of HO-1 by glucose deprivation in HepG2 hepatoma cells. Either N-acetylcysteine, an antioxidant, or deferoxamine, an iron chelator, resulted in a dose-dependent inhibition of HO-1 mRNA and protein induction during glucose deprivation, suggesting a redox- and iron-dependent mechanism. Inhibitors of electron-transport chain complex III, antimycin A and myxothiazol, the ATP synthase inhibitor oligomycin and ATP depletion with 2-deoxyglucose or glucosamine also blocked HO-1 induction. To address the involvement of ROS further, specifically H2O2, we showed that overexpression of catalase completely blocked HO-1 activation by glucose deprivation. In contrast, inhibition of nuclear factor κB, mitogen-activated protein kinase (MAPK), protein kinase A, protein kinase C, phosphoinositide 3-kinase, cyclo-oxygenase or cytosolic phospholipase A2, did not prevent HO-1 induction. These results demonstrate that activation of the HO-1 gene by glucose deprivation is mediated by a ‘glucose metabolic response’ pathway via generation of ROS and that the pathway requires a functional electron-transport chain.

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