New Control of Mitochondrial Membrane Potential and ROS Formation A Hypothesis

Lee, Icksoo; Bender, Elisabeth; Arnold, Susanne; Kadenbach, Bernhard

doi:10.1515/bc.2001.198

Cited by 91 publications

(73 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, ROS generation in mitochondria can be measured only when this potential decreases below Ϫ120 mV, which occurs under stressinduced increases of calcium ions or decreases of the ATP͞ADP ratio (26). Thus, this study also suggests that an operating respiratory chain is not involved in ROS generation (26). Further, the relevance of the mitochondrial respiratory chain as oxygen sensor was questioned in experiments with various cell lines defective in components of the electron-transport chain.…”

Section: Discussionmentioning

confidence: 81%

A Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression

Liu

Berchner‐Pfannschmidt

Möller

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

154

111

View full text Add to dashboard Cite

It has been proposed that hydroxyl radicals (⅐OH) generated in a perinuclear iron-dependent Fenton reaction are involved in O 2-dependent gene expression. Thus, it was the aim of this study to localize the cellular compartment in which the Fenton reaction takes place and to determine whether scavenging of ⅐OH can modulate hypoxia-inducible factor 1 (HIF-1)-dependent gene expression. The Fenton reaction was localized by using the nonfluorescent dihydrorhodamine (DHR) 123 that is irreversibly oxidized to fluorescent rhodamine 123 while scavenging ⅐OH together with gene constructs allowing fluorescent labeling of mitochondria, endoplasmic reticulum (ER), Golgi apparatus, peroxisomes, or lysosomes. A 3D two-photon confocal laser scanning microscopy showed ⅐OH generation in distinct hot spots of perinuclear ER pockets. This ER-based Fenton reaction was strictly pO 2-dependent.

show abstract

Section: Discussionmentioning

confidence: 81%

A Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression

Liu

Berchner‐Pfannschmidt

Möller

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

154

111

View full text Add to dashboard Cite

show abstract

“…8 -10 The release of the main mitochondrial proapoptotic protein, cytochrome c, is under the regulation of ROS. 11,12 In addition to the generation of ROS, NO is also generated in anticancer drug-and ␥-ray-treated cancer cells and reaction of ROS with NO is allowed in a favorable circumstance. 13,14 The reactant ONOO Ϫ vigorously damages cells by impairment of proteins and DNA.…”

mentioning

confidence: 99%

Tyrosine‐nitration of caspase 3 and cytochrome c does not suppress apoptosis induction in squamous cell carcinoma cells

Ueta

Kamatani

Yamamoto

et al. 2002

Intl Journal of Cancer

View full text Add to dashboard Cite

The influence of tyrosine nitration of cytochrome c and caspase 3 on apoptosis induction was investigated in an established squamous carcinoma cell line, OSC-4. The intracellular NO and O 2 ؊ levels were increased up to about 110 -120% and 140 -180% of the control levels, respectively, after the treatment of OSC-4 cells with 5-FU (100 g/ml), PLM (10 g/ml), CDDP (10 g/ml), or ␥-rays (20 Gy). The treatment of OSC-4 cells with ONOO ؊ (1 mM) and the above anticancer agents induced tyrosine nitration of 14, 32 kDa protein among others and nitration of tyrosine residues of cytochrome c and caspase 3 was identified by the Western blotting of immunoprecipitates obtained by antibodies to these proapoptotic proteins. When cytochrome c and procaspase 3 were treated with ONOO ؊ , tyrosine nitration was increased in a ONOO ؊ -dose dependent manner. Tyrosine nitration of cleaved (17 kDa) Key words: tyrosine-nitration; caspase 3; cytochrome c; apoptosis; squamous cell carcinoma cells; anticancer agentsSuccessful anticancer therapy with chemicals and radiation strongly depends on the strategy for differentiation and apoptosis induction of cancer cells. ROS induce apoptotic signals in cancer cells and apoptosis induction by anticancer drugs and ␥-rays is closely associated with intracellular ROS generation. [1][2][3][4][5][6][7] Apoptotic signals are transduced mainly through 2 pathways, one of which is originates from the mitochondria and the other is the Fas-associated route. 8 -10 The release of the main mitochondrial proapoptotic protein, cytochrome c, is under the regulation of ROS. 11,12 In addition to the generation of ROS, NO is also generated in anticancer drug-and ␥-ray-treated cancer cells and reaction of ROS with NO is allowed in a favorable circumstance. 13,14 The reactant ONOO Ϫ vigorously damages cells by impairment of proteins and DNA. [15][16][17][18][19] Inactivation of the proapoptotic proteins by ONOO Ϫ is therefore probable in chemoradiotherapy of cancers although the apoptosis-inducing activity of ONOO Ϫ has been demonstrated in multiple kinds of cancer cells. 20,21 NO reacts with molecular oxygen (O 2 ), O 2 Ϫ and transitional metals, yielding nitrogen dioxide (NO 2 ), ONOO Ϫ and metalnitrosyl adducts, respectively. 22-24 These reactants are highly reactive and exhibit a variety of physiological activities. 25 In many disorders including inflammatory diseases, the neurotoxicity of stroke, Alzheimer's disease, Parkinson's disease and multiple sclerosis, the highly reactive nitrogen chemicals, especially ONOO Ϫ , are deeply associated with the pathological degeneration of the tissues although the half life of ONOO Ϫ is very short, less than one second in the physiological condition. 26,27 ONOO Ϫ has a potential to cause DNA-strand breaks, lipid peroxidation and diverse modification of cellular molecules such as oxidation of thiol and methionine and nitration of tyrosine and tryptophane. 28 In these modifications, tyrosine nitration has been extensively explored with the aim of analysis of the cytotoxic mec...

show abstract

“…In our experiments, we failed to reproduce the initial data from Lee, where allosteric inhibition of CytOx was induced by Protein kinase A and switched off by Phosphatase PP1 9, 10. Various factors, for example the presence of phosphatases/phosphatase inhibitors or protein kinases/protein kinase inhibitors were used in the polarographic measurements to initiate or modify allosteric inhibition of CytOx, which however, yielded no clear results.…”

Section: Introductionmentioning

confidence: 71%

“…However, low Ψm values are found in perfused rat hearts (100–140 mV) 47, 48, cultured fibroblasts (105 mV) and neuroblastoma cells (81 mV) 49. Kadenbach's theory explained this discrepancy in a new hypothesis for the regulation of mitochondrial energy metabolism in living cells 9, 10, 50, 51, 52, 53. This hypothesis explains the increase of Ψm and the formation of ROS in mitochondria under stress conditions and excessive work 54.…”

Section: Ros Have Double Functionsmentioning

confidence: 99%

Revisiting Kadenbach: Electron flux rate through cytochrome c‐oxidase determines the ATP‐inhibitory effect and subsequent production of ROS

et al. 2016

View full text Add to dashboard Cite

Mitochondrial respiration is the predominant source of ATP. Excessive rates of electron transport cause a higher production of harmful reactive oxygen species (ROS). There are two regulatory mechanisms known. The first, according to Mitchel, is dependent on the mitochondrial membrane potential that drives ATP synthase for ATP production, and the second, the Kadenbach mechanism, is focussed on the binding of ATP to Cytochrome c Oxidase (CytOx) at high ATP/ADP ratios, which results in an allosteric conformational change to CytOx, causing inhibition. In times of stress, ATP‐dependent inhibition is switched off and the activity of CytOx is exclusively determined by the membrane potential, leading to an increase in ROS production. The second mechanism for respiratory control depends on the quantity of electron transfer to the Heme aa3 of CytOx. When ATP is bound to CytOx the enzyme is inhibited, and ROS formation is decreased, although the mitochondrial membrane potential is increased.

show abstract

New Control of Mitochondrial Membrane Potential and ROS Formation A Hypothesis

Cited by 91 publications

References 49 publications

A Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression

A Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression

Tyrosine‐nitration of caspase 3 and cytochrome c does not suppress apoptosis induction in squamous cell carcinoma cells

Revisiting Kadenbach: Electron flux rate through cytochrome c‐oxidase determines the ATP‐inhibitory effect and subsequent production of ROS

Contact Info

Product

Resources

About