[18] Mitochondrial l-malate dehydrogenase of beef heart

Englard, Sasha; Siegel, Lewis

doi:10.1016/0076-6879(69)13022-0

Cited by 88 publications

(40 citation statements)

References 11 publications

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“…Aconitase activity was measured as described (17). Malate dehydrogenase was measured in isolated mitochondria as described (18), as was succinate dehydrogenase (19).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Fe-S cluster biosynthesis decreases mitochondrial iron export: Evidence that Yfh1p affects Fe-S cluster synthesis

Chen

Hemenway

Kaplan

2002

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

144

114

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Decreased expression of Yfh1p in the budding yeast, Saccharomyces cerevisiae, and the orthologous human gene frataxin results in respiratory deficiency and mitochondrial iron accumulation. The absence of Yfh1p decreases mitochondrial iron export. We demonstrate that decreased expression of Nfs1p, the yeast cysteine desulfurase that plays a central role in Fe-S cluster synthesis, also results in mitochondrial iron accumulation due to decreased export of mitochondrial iron. In the absence of Yfh1p, activity of Fe-Scontaining enzymes (aconitase, succinate dehydrogenase) is decreased, whereas the activity of a non-Fe-S-containing enzyme (malate dehydrogenase) is unaffected. Aconitase protein was abundant even though the activity of aconitase was decreased in both aerobic and anaerobic conditions. These results demonstrate a direct role of Yfh1p in the formation of Fe-S clusters and indicate that mitochondrial iron export requires Fe-S cluster biosynthesis.F rataxin is a highly conserved protein found in all eukaryotes.The protein is encoded by a nuclear gene and is localized in the mitochondrial matrix. Deficits in frataxin protein result in Friedreich ataxia, a neurologic and cardiac disorder (1). Deletion of Yfh1p, the frataxin orthologue in yeast, leads to a respiratory defect resulting from excessive mitochondrial iron accumulation, which increases oxidant damage (2). The increase in mitochondrial iron is caused by malregulation of the mitochondrial iron cycle (3). Mitochondrial iron accumulation is only seen when cytosolic iron levels are high. Reduction in cytosolic iron due to either low-iron media (3, 4), deletion of genes required for high-affinity iron transport (3), or increased vacuolar iron transport (5), prevents excessive mitochondrial iron accumulation and will preserve respiratory activity in ⌬yfh1 cells.In yeast, the proteins involved in Fe-S cluster synthesis are compartmentalized in the mitochondria where Fe-S clusters are synthesized for use both in mitochondria and for export to cytosolic proteins (6). Excessive mitochondrial iron is also seen as a result of deletion of genes required for synthesis of Fe-S clusters (for review, see ref. 6). For example, decreased expression of Nfs1p, the cysteine desulfurase (7, 8), Isu1p, a putative scaffolding protein (9), Yah1p, a putative ferredoxin (10), and Arh1p, a putative ferredoxin reductase (11), results in mitochondrial iron accumulation. In addition, reduced expression of Atm1p, a putative mitochondrial Fe-S exporter, also leads to accumulation of toxic levels of mitochondrial iron (7). The mechanism by which iron accumulates has not been elucidated. Herein, we describe that reduced expression of a critical enzyme involved in Fe-S synthesis, Nfs1p, results in mitochondrial iron accumulation through decreased mitochondrial iron export, similar to that seen in ⌬yfh1 cells (3). This result indicates that mitochondrial iron export depends on Fe-S cluster synthesis, suggesting that Yfh1p may play a role in Fe-S cluster synthesis. To test this hypothesis...

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“…Aconitase activity was measured as described (17). Malate dehydrogenase was measured in isolated mitochondria as described (18), as was succinate dehydrogenase (19).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Fe-S cluster biosynthesis decreases mitochondrial iron export: Evidence that Yfh1p affects Fe-S cluster synthesis

Chen

Hemenway

Kaplan

2002

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

144

114

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“…Isocitrate dehydrogenase (Cook & Sanwal, 1969), aketoglutarate dehydrogenase (Nichols et al, 1994) and malate dehydrogenase (Englard & Siegel, 1969) activities in the soluble fractions were assayed as NADH-producing steps in the TCA cycle. NADH dehydrogenase (complex I) (Fang & Beattie, 2003), cytochrome c oxidase (complex IV) (Wang et al, 2004) and ATP synthase (complex V) (Kagawa & Yoshida, 1979) were assayed in the membrane fraction.…”

Section: Methodsmentioning

confidence: 99%

The crucial role of mitochondrial regulation in adaptive aluminium resistance in Rhodotorula glutinis

et al. 2008

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Rhodotorula glutinis IFO1125 was found to acquire increased aluminium (Al) resistance from 50 mM to more than 5 mM by repetitive culturing with stepwise increases in Al concentration at pH 4.0. To investigate the mechanism underlying this novel phenomenon, wild-type and Alresistant cells were compared. Neither cell type accumulated the free form of Al (Al 3+ ) added to the medium. Transmission electron microscopic analyses revealed a greater number of mitochondria in resistant cells. The formation of small mitochondria with simplified cristae structures was observed in the wild-type strain grown in the presence of Al and in resistant cells grown in the absence of Al. Addition of Al to cells resulted in high mitochondrial membrane potential and concomitant generation of reactive oxygen species (ROS). Exposure to Al also resulted in elevated levels of oxidized proteins and oxidized lipids. Addition of the antioxidants a-tocopherol and ascorbic acid alleviated the Al toxicity, suggesting that ROS generation is the main cause of Al toxicity. Differential display analysis indicated upregulation of mitochondrial genes in the resistant cells. Resistant cells were found to have 2.5-to 3-fold more mitochondrial DNA (mtDNA) than the wild-type strain. Analysis of tricarboxylic acid cycle and respiratory-chain enzyme activities in wild-type and resistant cells revealed significantly reduced cytochrome c oxidase activity and resultant high ROS production in the latter cells. Taken together, these data suggest that the adaptive increased resistance to Al stress in resistant cells resulted from an increased number of mitochondria and increased mtDNA content, as a compensatory response to reduced respiratory activity caused by a deficiency in complex IV function.

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“…Malate dehydrogenase (MDH) catalyses the oxidation of malate to oxalacetate by reducing nicotinamide adenine dinucleotide (NAD+) to NADH [16] In the next sections we consider an automated tool that makes the discovery of computational properties from enzymes more feasible. This achieved through minimising both the chemical resources per experiment and the number of experiments required to characterise a behaviour.…”

Section: Enzymatic Computingmentioning

confidence: 99%

Enabling the discovery of computational characteristics of enzyme dynamics

Jones

Lovell

Gunn

et al. 2012

2012 IEEE Congress on Evolutionary Computation

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Abstract-Biology demonstrates powerful information processing capabilities. Of particular interest are enzymes, which process information in highly complex dynamic environments. Exploring the information processing characteristics of an enzyme by selectively altering its environment may lead to the discovery of new modes of computation. The physical experiments required to perform such exploration are combinatorial in nature. Thus resource consumption, both time and money, poses major limiting factors on any exploratory work. New tools are required to mitigate these factors. One such tool is lab-on-chip based autonomous experimentation system, where a microfluidic experimentation platform is driven by machine learning algorithms. The lab-onchip approach provides an automated platform that can perform complex protocols, which is also capable of reducing the resource cost of experimentation. The machine learning algorithms provide intelligent experiment selection that reduces the number of experiments required for discovery. Here we discuss development of the experimentation platform and machine learning software that will lead to fully autonomous characterisation of enzymes.

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[18] Mitochondrial l-malate dehydrogenase of beef heart

Cited by 88 publications

References 11 publications

Inhibition of Fe-S cluster biosynthesis decreases mitochondrial iron export: Evidence that Yfh1p affects Fe-S cluster synthesis

Inhibition of Fe-S cluster biosynthesis decreases mitochondrial iron export: Evidence that Yfh1p affects Fe-S cluster synthesis

The crucial role of mitochondrial regulation in adaptive aluminium resistance in Rhodotorula glutinis

Enabling the discovery of computational characteristics of enzyme dynamics

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