A comparative study of the regulation of Ca2+ of the activities of the 2-oxoglutarate dehydrogenase complex and NAD+-isocitrate dehydrogenase from a variety of sources

McCormack, James G.; Denton, R M

doi:10.1042/bj1960619

Cited by 89 publications

(52 citation statements)

References 27 publications

(31 reference statements)

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“…Thus, copper-induced calcium release activates mitochondrial NADH-synthesizing enzymes, leading to an increase in NADH, which may enter in mitochondrial complex I increasing electron transport and production of superoxide anions that are dismutated to H 2 O 2 by SOD. In this sense, it is important to mention that NADH-synthesizing enzymes IDH and OGDH are directly activated by calcium in mammalian cells , whereas PDH activity is indirectly activated by calcium in mammalian cells and in plants (McCormack and Denton, 1981;Budde et al, 1988;Denton, 2009). Thus, the calcium-dependent regulation of PDH activity in U. compressa differs from what was observed in other eukaryotes, because this enzyme is directly activated by calcium.…”

Section: Copper-induced H 2 O 2 Synthesis Is Dependent On Calcium Relmentioning

confidence: 46%

“…In contrast, pyruvate dehydrogenase (PDH) is activated by a calcium-dependent phosphatase and, thus, is indirectly activated by calcium (Budde et al, 1988;Denton, 2009). In plants, PDH, IDH, and OGDH activities are indirectly regulated by calcium, and their activation is dependent on calmodulins (CaMs; McCormack and Denton, 1981;Miernyk et al, 1987;Budde et al, 1988). In addition, it was shown that calcium-dependent activation of Krebs cycle enzymes leads to an increase in NADH concentration enhancing mitochondrial electron transport and, thus, production of superoxide anions and H 2 O 2 in human cells (Brookes et al, 2004;CamelloAlmaraz et al, 2006;Hidalgo and Donoso, 2008).…”

mentioning

confidence: 99%

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Cross Talk among Calcium, Hydrogen Peroxide, and Nitric Oxide and Activation of Gene Expression Involving Calmodulins and Calcium-Dependent Protein Kinases in Ulva compressa Exposed to Copper Excess

et al. 2012

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To analyze the copper-induced cross talk among calcium, nitric oxide (NO), and hydrogen peroxide (H2O2) and the calcium-dependent activation of gene expression, the marine alga Ulva compressa was treated with the inhibitors of calcium channels, ned-19, ryanodine, and xestospongin C, of chloroplasts and mitochondrial electron transport chains, 3-(3,4-dichlorophenyl)-1,1-dimethylurea and antimycin A, of pyruvate dehydrogenase, moniliformin, of calmodulins, N-(6-aminohexyl)-5-chloro-1-naphtalene sulfonamide, and of calcium-dependent protein kinases, staurosporine, as well as with the scavengers of NO, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, and of H2O2, ascorbate, and exposed to a sublethal concentration of copper (10 μm) for 24 h. The level of NO increased at 2 and 12 h. The first peak was inhibited by ned-19 and 3-(2,3-dichlorophenyl)-1,1-dimethylurea and the second peak by ned-19 and antimycin A, indicating that NO synthesis is dependent on calcium release and occurs in organelles. The level of H2O2 increased at 2, 3, and 12 h and was inhibited by ned-19, ryanodine, xestospongin C, and moniliformin, indicating that H2O2 accumulation is dependent on calcium release and Krebs cycle activity. In addition, pyruvate dehydrogenase, 2-oxoxglutarate dehydrogenase, and isocitrate dehydrogenase activities of the Krebs cycle increased at 2, 3, 12, and/or 14 h, and these increases were inhibited in vitro by EGTA, a calcium chelating agent. Calcium release at 2, 3, and 12 h was inhibited by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide and ascorbate, indicating activation by NO and H2O2. In addition, the level of antioxidant protein gene transcripts decreased with N-(6-aminohexyl)-5-chloro-1-naphtalene sulfonamide and staurosporine. Thus, there is a copper-induced cross talk among calcium, H2O2, and NO and a calcium-dependent activation of gene expression involving calmodulins and calcium-dependent protein kinases.

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Section: Copper-induced H 2 O 2 Synthesis Is Dependent On Calcium Relmentioning

confidence: 46%

mentioning

confidence: 99%

Cross Talk among Calcium, Hydrogen Peroxide, and Nitric Oxide and Activation of Gene Expression Involving Calmodulins and Calcium-Dependent Protein Kinases in Ulva compressa Exposed to Copper Excess

et al. 2012

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“…Elevated Ca 2+ levels have also been observed in ASD brains, and the excess Ca 2+ could activate the neuronal aspartate/glutamate carrier of the mitochondrial NADH shuttle system (68) and the tricarboxylic acid cycle dehydrogenases (69,70). Both of these effects would drive excessive reducing equivalents into the ETC, stimulating mitochondrial ROS production, oxidative stress, mitochondrial damage, and synaptic loss.…”

Section: The Ndna and Mtdna Genetics Of "Complex" Diseasesmentioning

confidence: 99%

A mitochondrial bioenergetic etiology of disease

Wallace¹

2013

J. Clin. Invest.

281

266

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“…Sources of materials are as for Denton et al (1984) (Denton et al, 1972;Severson et al, 1974; As expected on the basis of previous studies on other rat tissues (see McCormack & Denton, 1981b Mitochondria were prepared from paired fat-pads incubated (as in Fig. 1) with or without 50nM-insulin.…”

Section: Methodsmentioning

confidence: 99%

“…Studies, mainly with rat heart, have indicated tissues (see , 1981 ,1978aMcCormack & Denton, 1979,1981b dehydrogenase activity can be demonstrated withthe concentration of effector required for a half-maximal in coupled rat heart mitochondria exposed to response.…”

mentioning

confidence: 99%

Role of Ca2+ ions in the regulation of intramitochondrial metabolism in rat epididymal adipose tissue. Evidence against a role for Ca2+ in the activation of pyruvate dehydrogenase by insulin

Marshall¹,

McCormack²,

Denton³

1984

Biochemical Journal

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1. The sensitivity of rat epididymal-adipose-tissue pyruvate dehydrogenase phosphate phosphatase, NAD+-isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase to Ca2 + ions was studied both in mitochondrial extracts and within intact coupled mitochondria. It is concluded that all three enzymes may be activated by increases in the intramitochondrial concentration of Ca2 + and that the distribution of Ca2 + across the mitochondrial inner membrane is determined, as in rat heart mitochondria, by the relative activities of a uniporter (which transports Ca2 + into mitochondria and is inhibited by Mg2 + and Ruthenium Red) and an antiporter (which allows Ca2 + to leave mitochondria in exchange for Na+ and is inhibited by diltiazem). 2. Previous studies with incubated fat-cell mitochondria have indicated that the increases in the amount of active non-phosphorylated pyruvate dehydrogenase in rat epididymal tissue exposed to insulin are the result of activation of pyruvate dehydrogenase phosphate phosphatase. In the present studies, no changes in the activity of the phosphatase were found in extracts of mitochondria, and thus it seemed likely that insulin altered the intramitochondrial concentration of some effector of the phosphatase. 3. Incubation of rat epididymal adipose tissue with medium containing a high-concentration of CaCl2 (5 mM) was found to increase the active form of pyruvate dehydrogenase to much the same extent as insulin. However, the increases caused by high [Ca2 + ] in the medium were blocked by Ruthenium Red, whereas those caused by insulin were not. Moreover, whereas the increases resulting from both treatments persisted during the preparation of mitochondria and their subsequent incubation in the absence of Na+, only the increases caused by treatment of the tissue with insulin persisted when the mitochondria were incubated in the presence of Na+ under conditions where the mitochondria are largely depleted of Ca2 +. 4. It is concluded that insulin does not act by increasing the intramitochondrial concentration of Ca2 +. This conclusion was supported by finding no increases in the activities of the other two Ca2+-responsive intramitochondrial enzymes (NAD+-isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase) in mitochondria prepared from insulin-treated tissue compared with controls.

show abstract

A comparative study of the regulation of Ca2+ of the activities of the 2-oxoglutarate dehydrogenase complex and NAD+-isocitrate dehydrogenase from a variety of sources

Cited by 89 publications

References 27 publications

Cross Talk among Calcium, Hydrogen Peroxide, and Nitric Oxide and Activation of Gene Expression Involving Calmodulins and Calcium-Dependent Protein Kinases in Ulva compressa Exposed to Copper Excess

Cross Talk among Calcium, Hydrogen Peroxide, and Nitric Oxide and Activation of Gene Expression Involving Calmodulins and Calcium-Dependent Protein Kinases in Ulva compressa Exposed to Copper Excess

A mitochondrial bioenergetic etiology of disease

Role of Ca2+ ions in the regulation of intramitochondrial metabolism in rat epididymal adipose tissue. Evidence against a role for Ca2+ in the activation of pyruvate dehydrogenase by insulin

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