Localization of the α‐oxoacid dehydrogenase multienzyme complexes within the mitochondrion

Maas, Edith; Bisswanger, Hans

doi:10.1016/0014-5793(90)80840-f

Cited by 41 publications

(30 citation statements)

References 10 publications

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“…However, the relationship between KGDHC activity and mitochondrial damage per se is much less clear. KGDHC is an integral mitochondrial enzyme tightly bound to the inner mitochondrial membrane on the matrix side (Maas and Bisswanger, 1990). It binds (specifically) to complex I of the mitochondrial respiratory chain (Sumegi and Srere, 1984) and may form a part of the TCA cycle enzyme supercomplex (Lyubarev and Kurganov, 1989).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial α-Ketoglutarate Dehydrogenase Complex Generates Reactive Oxygen Species

Starkov¹,

Fiskum²,

Chinopoulos³

et al. 2004

J. Neurosci.

641

472

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Mitochondria-produced reactive oxygen species (ROS) are thought to contribute to cell death caused by a multitude of pathological conditions. The molecular sites of mitochondrial ROS production are not well established but are generally thought to be located in complex I and complex III of the electron transport chain. We measured H 2 O 2 production, respiration, and NADPH reduction level in rat brain mitochondria oxidizing a variety of respiratory substrates. Under conditions of maximum respiration induced with either ADP or carbonyl cyanide p-trifluoromethoxyphenylhydrazone, ␣-ketoglutarate supported the highest rate of H 2 O 2 production. In the absence of ADP or in the presence of rotenone, H 2 O 2 production rates correlated with the reduction level of mitochondrial NADPH with various substrates, with the exception of ␣-ketoglutarate. Isolated mitochondrial ␣-ketoglutarate dehydrogenase (KGDHC) and pyruvate dehydrogenase (PDHC) complexes produced superoxide and H 2 O 2 . NAD ϩ inhibited ROS production by the isolated enzymes and by permeabilized mitochondria. We also measured H 2 O 2 production by brain mitochondria isolated from heterozygous knock-out mice deficient in dihydrolipoyl dehydrogenase (Dld). Although this enzyme is a part of both KGDHC and PDHC, there was greater impairment of KGDHC activity in Dld-deficient mitochondria. These mitochondria also produced significantly less H 2 O 2 than mitochondria isolated from their littermate wild-type mice. The data strongly indicate that KGDHC is a primary site of ROS production in normally functioning mitochondria.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial α-Ketoglutarate Dehydrogenase Complex Generates Reactive Oxygen Species

Starkov¹,

Fiskum²,

Chinopoulos³

et al. 2004

J. Neurosci.

641

472

View full text Add to dashboard Cite

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“…Upon inactivation, isolated aconitase induces production of hydroxyl radical, most likely mediated by released Fe 2+ [36]. 7) α α Ketoglutarate dehydrogenase complex (KGDHC, aka 2 oxoglutarate dehydrogenase) is tightly associated with the matrix side of the inner membrane [37] [38,39] and in isolated mouse brain mitochondria c, cytochrome c; C III, Complex III; MnSOD, mitochondrial manganese superoxide dismutase; Cat, catalase; SDH, succinate dehydro genase; ACO, aconitase; Prx3 red , peroxiredoxin reduced; Prx3 ox , peroxiredoxin oxidized; Q, coenzyme Q; DHOH, dihydroorotate dehy drogenase; KGDHC, α ketoglutarate dehydrogenase complex; αGDH, α glycerophosphate dehydrogenase; PDHC, pyruvate dehydroge nase complex; IDH, isocitric dehydrogenase, NAD + dependent; Trx2 red , thioredoxin 2 reduced; Trx2 ox , thioredoxin 2 oxidized; Grx2 red , glutaredoxin 2 reduced; Grx2 ox , glutaredoxin 2 oxidized; TrxR2, thioredoxin 2 reductase; MDH, malate dehydrogenase; IDH 1 , isocitric dehydrogenase, NADP + dependent; ME, malic enzyme, NADP + dependent; GR, glutathione reductase; GSH, reduced glutathione; GS SG, oxidized glutathione dipeptide; GPx, glutathione peroxidase; PGPx, phospholipid hydroperoxide glutathione peroxidase; C I, Complex I; TH, transhydrogenase; Cyt. b5 reductase, cytochrome b5 reductase; MAOs, monoamine oxidases A and B; OM, outer mito chondrial membrane; IM, inner mitochondrial membrane.…”

Section: Multiplicity Of Ros Producing Sources In Mitochondriamentioning

confidence: 99%

Mitochondrial metabolism of reactive oxygen species

Andreyev

Kushnareva

Starkov

2005

Biochemistry (Moscow)

1,135

957

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Oxidative stress is considered a major contributor to etiology of both "normal" senescence and severe pathologies with serious public health implications. Mitochondria generate reactive oxygen species (ROS) that are thought to augment intracellular oxidative stress. Mitochondria possess at least nine known sites that are capable of generating superoxide anion, a progenitor ROS. Mitochondria also possess numerous ROS defense systems that are much less studied. Studies of the last three decades shed light on many important mechanistic details of mitochondrial ROS production, but the bigger picture remains obscure. This review summarizes the current knowledge about major components involved in mitochondrial ROS metabolism and factors that regulate ROS generation and removal. An integrative, systemic approach is applied to analysis of mitochondrial ROS metabolism, which is now dissected into mitochondrial ROS production, mitochondrial ROS removal, and mitochondrial ROS emission. It is suggested that mitochondria augment intracellular oxidative stress due primarily to failure of their ROS removal systems, whereas the role of mitochondrial ROS emission is yet to be determined and a net increase in mitochondrial ROS production in situ remains to be demonstrated.

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“…The protein interacts selectively and non-covalently with thiamine pyrophosphate, and acts as a coenzyme of several carboxylases and decarboxylases, transketolases, and alpha-oxoacid dehydrogenases. These enzymes are related to energy metabolism, pentose phosphate pathaway, glycolysis and mitochondria (Maas and Bisswanger 1990). In the case of P. indica we suggest that this gene may be involved in energy metabolism during the salt-stress condition.…”

Section: Discussionmentioning

confidence: 99%

Isolation of genes conferring salt tolerance from Piriformospora indica by random overexpression in Escherichia coli

Gahlot

Joshi

Singh

et al. 2015

World J Microbiol Biotechnol

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Piriformospora indica, a root endophytic fungus identified in the Indian Thar desert, colonizes the roots of plants and provides resistance towards biotic stress as well as tolerance to abiotic stress in the plants. Despite its positive impact on the host, little is known about the P. indica genes that are involved in salt stress tolerance. Therefore this study was conducted to identify and isolate high salinity-tolerance genes from P. indica. Thirty-six salinity-tolerance genes were obtained by functional screening, based on random over expression of a P. indica cDNA library in Escherichia coli grown on medium supplemented with 0.6 M NaCl. The salinity tolerance conferred by these 36 genes in bacteria was further confirmed by using another strain of E. coli (DH5α) transformants. However when the expression of these 36 genes was analysed in P. indica using quantitative RT-PCR, we found only six genes were up-regulated by salt stress. These six genes are involved in different cellular processes, such as metabolism, energy and biosynthetic processes, DNA repair, regulation of protein turnover, transport and salt stress tolerance. This work presents the basis for further molecular analyses of the mechanisms of salt tolerance in P. indica and for the use of this endophyte to confer salt tolerance to plants.

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Localization of the α‐oxoacid dehydrogenase multienzyme complexes within the mitochondrion

Cited by 41 publications

References 10 publications

Mitochondrial α-Ketoglutarate Dehydrogenase Complex Generates Reactive Oxygen Species

Mitochondrial α-Ketoglutarate Dehydrogenase Complex Generates Reactive Oxygen Species

Mitochondrial metabolism of reactive oxygen species

Isolation of genes conferring salt tolerance from Piriformospora indica by random overexpression in Escherichia coli

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