scholarly journals Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II in cell death initiation

2015 ◽  
Vol 6 (5) ◽  
pp. e1749-e1749 ◽  
Author(s):  
K Kluckova ◽  
M Sticha ◽  
J Cerny ◽  
T Mracek ◽  
L Dong ◽  
...  
Keyword(s):  
Cell Death ◽  
Binding Site ◽  
Mitochondrial Complex ◽  
Complex Ii ◽  
Site Mutagenesis ◽  
Ubiquinone Binding

scholarly journals Inhibitors of ROS production by the ubiquinone-binding site of mitochondrial complex I identified by chemical screening

2013 ◽  
Vol 65 ◽  
pp. 1047-1059 ◽  
Author(s):  
Adam L. Orr ◽  
Deepthi Ashok ◽  
Melissa R. Sarantos ◽  
Tong Shi ◽  
Robert E. Hughes ◽  
...  
Keyword(s):  
Binding Site ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Ros Production ◽  
Mitochondrial Complex ◽  
Chemical Screening ◽  
Ubiquinone Binding

scholarly journals The Nitrone Disodium 2,4-Sulphophenyl-N-Tert-Butylnitrone is Without Cytoprotective Effect on Sodium Nitroprusside-Induced Cell Death in N1E-115 Neuroblastoma Cells in vitro

2007 ◽  
Vol 28 (1) ◽  
pp. 24-28 ◽  
Author(s):  
Atticus H Hainsworth ◽  
Nasrin Bhuiyan ◽  
A Richard Green
Keyword(s):  
Cell Death ◽  
Free Radical ◽  
Sodium Nitroprusside ◽  
Neurovascular Unit ◽  
Neuroblastoma Cells ◽  
Mitochondrial Complex ◽  
Complex Ii ◽  
Radical Trapping

Disodium 2,4-sulphophenyl- N-tert-butylnitrone (NXY-059) is a novel free radical-trapping compound that is neuroprotective in both rodent and primate models of acute ischaemic stroke. Neuroprotection in vitro by NXY-059 has not been reported previously, and we have now investigated whether such an effect can be detected using a simple cell culture model of neurotoxicity. Neuron-like cells of the neuroblastoma-derived clonal cell line N1E-115 were exposed to the free radical-generating agent sodium nitroprusside (SNP), which produced a concentration-dependent reduction in mitochondrial complex II activity 24 h later (EC50 approximately 100 micromolar). Cell death induced by SNP (100 micromolar), assessed either by an increased proportion of apoptotic nuclear morphology or by mitochondrial complex II activity, was inhibited by a cocktail of known antioxidants (ascorbate, reduced glutathione, and dithiothreitol, all at 100 micromolar) but not by NXY-059 at a concentration known to be neuroprotective in vivo (300 micromolar). Disodium 2,4-sulphophenyl- N-tert-butylnitrone was also without effect on H2O2-mediated cytotoxicity. These results support recent data suggesting that in vivo NXY-059 probably acts at the neurovascular unit rather than at an intracellular site as a neuroprotective agent.

scholarly journals The Emerging Role of Succinate Dehyrogenase Genes (SDHx) in Tumorigenesis

2019 ◽  
Author(s):  
Elham Nazar ◽  
Fatemeh Khatami ◽  
Hiva Saffar ◽  
Seyed Mohammad Tavangar
Keyword(s):  
Normal Cell ◽  
Neoplastic Transformation ◽  
Genetic Alterations ◽  
Epigenetic Changes ◽  
Epigenetic Alterations ◽  
Mitochondrial Complex ◽  
Complex Ii ◽  
Hypoxic Conditions ◽  
Sdh Mutation

Transformation of a normal cell to cancerous one is dependent on the accumulation of several genetic and epigenetic alterations. One of the candidate driver genetic alterations can happen in succinate dehydrogenases (SDHx) coding gene include SDHA, SDHB, SDHC, SDHD, and SDHAF2.  The most important SDH mutation is in the SDHD gene, which encodes the smallest subunit of mitochondrial complex II (SDH). It has key function both in familial and non-familial hereditary paraganglioma/phaeochromocytoma syndrome (HPGL/PCC). SDHx genes mutations can have resulted in genetic and epigenetic changes like histone hypermethylation. These properties can lead to succinate-mediated inhibition of α-ketoglutarate-dependent dioxygenases. So hypoxic conditions can generate subsequent neoplastic transformation, and in this review, we are presenting the role of SDHx in several malignancies.

scholarly journals Complex effects of pH on ROS from mitochondrial complex II driven complex I reverse electron transport challenge its role in tissue reperfusion injury

2020 ◽  
Author(s):  
Alexander S. Milliken ◽  
Chaitanya A. Kulkarni ◽  
Paul S. Brookes
Keyword(s):  
Electron Transport ◽  
Complex I ◽  
Ischemia Reperfusion ◽  
Mitochondrial Complex ◽  
Complex Ii ◽  
Effects Of Ph ◽  
Cellular Necrosis ◽  
Reverse Electron Transport ◽  
The Impact

ABSTRACTGeneration of mitochondrial reactive oxygen species (ROS) is an important process in triggering cellular necrosis and tissue infarction during ischemia-reperfusion (IR) injury. Ischemia results in accumulation of the metabolite succinate. Rapid oxidation of this succinate by mitochondrial complex II (Cx-II) during reperfusion reduces the co-enzyme Q (Co-Q) pool, thereby driving electrons backward into complex-I (Cx-I), a process known as reverse electron transport (RET), which is thought to be a major source of ROS. During ischemia, enhanced glycolysis results in an acidic cellular pH at the onset of reperfusion. While the process of RET within Cx-I is known to be enhanced by a high mitochondrial trans-membrane ΔpH, the impact of pH itself on the integrated process of Cx-II to Cx-I RET has not been fully studied. Using isolated mitochondria under conditions which mimic the onset of reperfusion (i.e., high [ADP]). We show that mitochondrial respiration (state 2 and state 3) as well as isolated Cx-II activity are impaired at acidic pH, whereas the overall generation of ROS by Cx-II to Cx-I RET was insensitive to pH. Together these data indicate that the acceleration of Cx-I RET ROS by ΔpH appears to be cancelled out by the impact of pH on the source of electrons, i.e. Cx-II. Implications for the role of Cx-II to Cx-I RET derived ROS in IR injury are discussed.

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