Postnatal Development of the Complexes of the Electron Transport Chain in Synaptic Mitochondria from Rat Brain

Almeida, Ángeles; Brooks, Karen; Sammut, Ivan A.; Keelan, J; Davey, Gavin P.; Clark, JB; Bates, Timothy E.

doi:10.1159/000111289

Cited by 43 publications

(25 citation statements)

References 22 publications

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“…Diverse developmental patterns of mitochondrial activity during post-natal brain development, however, also have been reported. For example, it has been reported complex I activity does not change during postnatal development, complex IV activity peaks a p20, and complex V activity increases linearly from p10 to p60 in the brain (Almeida et al 1995). These complex developmental patterns have also been previously reported for the expression of similar functional mitochondrial proteins.…”

Section: Genome Research 1381supporting

confidence: 63%

“…It has been shown that an increase in activity of mitochondrial enzymes does occur during postnatal development (Szutowicz et al 1982;Bukato et al 1992;Almeida et al 1995). Although enzyme activity and expression do not necessarily correspond, we observed significant increases in the expression of mitochondrial proteins from p1 to p45 that correspond to reports on enzyme activity.…”

Section: Genome Research 1381supporting

confidence: 51%

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Quantification of the synaptosomal proteome of the rat cerebellum during post-natal development

McClatchy

Liao²,

Park³

et al. 2007

Genome Res.

100

110

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Large-scale proteomic analysis of the mammalian brain has been successfully performed with mass spectrometry techniques, such as Multidimensional Protein Identification Technology (MudPIT), to identify hundreds to thousands of proteins. Strategies to efficiently quantify protein expression levels in the brain in a large-scale fashion, however, are lacking. Here, we demonstrate a novel quantification strategy for brain proteomics called SILAM (Stable Isotope Labeling in Mammals). We utilized a 15 N metabolically labeled rat brain as an internal standard to perform quantitative MudPIT analysis on the synaptosomal fraction of the cerebellum during post-natal development. We quantified the protein expression level of 1138 proteins in four developmental time points, and 196 protein alterations were determined to be statistically significant. Over 50% of the developmental changes observed have been previously reported using other protein quantification techniques, and we also identified proteins as potential novel regulators of neurodevelopment. We report the first large-scale proteomic analysis of synaptic development in the cerebellum, and we demonstrate a useful quantitative strategy for studying animal models of neurological disease.

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Section: Genome Research 1381supporting

confidence: 63%

Section: Genome Research 1381supporting

confidence: 51%

Quantification of the synaptosomal proteome of the rat cerebellum during post-natal development

McClatchy

Liao²,

Park³

et al. 2007

Genome Res.

100

110

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“…In this study, complex I in the synaptosomal mitochondria was inhibited by only ϳ10% before a decrease in oxygen consumption was observed, which is more in accordance with the level calculated for synaptic mitochondria, as would be expected, because a similar sample of mitochondria exists in isolated synaptic mitochondria preparations as in the synaptosomal preparations. A previous study showed that complex I activity was 36% lower in synaptic mitochondria than in nonsynaptic mitochondria (25), which may somewhat explain the lower thresholds obtained in synaptic and synaptosomal mitochondria when compared with nonsynaptic mitochondria. Similarly, a recent study found that complex I activity in C57BL/6J mouse brain synaptic mitochondria was 45% lower than that in nonsynaptic mitochondria (26).…”

Section: E (Error Bars)mentioning

confidence: 87%

Complex I Is Rate-limiting for Oxygen Consumption in the Nerve Terminal

Telford

Kilbride

Davey

2009

Journal of Biological Chemistry

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Metabolic control analysis was used to determine the spread of control exerted by the electron transport chain complexes over oxygen consumption rates in the nerve terminal. Oxygen consumption rates and electron transport chain complex activities were titrated with appropriate inhibitors to determine the flux control coefficients and the inhibition thresholds in rat brain synaptosomes. The flux control coefficients for complex I, complex II/III, complex III, and complex IV were found to be 0.30 ؎ 0.07, 0.20 ؎ 0.03, 0.20 ؎ 0.05, and 0.08 ؎ 0.05, respectively. Inhibition thresholds for complex I, complex II/III, complex III, and complex IV activities were determined to be ϳ10, ϳ30, ϳ35, and 50 -65%, respectively, before major changes in oxygen consumption rates were observed. These results indicate that, of the electron transport chain components, complex I exerts a high level of control over synaptosomal bioenergetics, suggesting that complex I deficiencies that are present in neurodegenerative disorders, such as Parkinson disease, are sufficient to compromise oxygen consumption in the synaptosomal model of the nerve terminal.

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“…Second, as energy demand and oxygen consumption increase postnatally, the activities of many mitochondrial enzymes involved in energy metabolism are gradually increased (Kalous, et al, 2001). These enzymes include adenine nucleotide translocase (Schonfeld and Bohnensack, 1995), creatine kinase (Holtzman, et al, 1993, Schonfeld andReiser, 2007), malic enzyme (Bukato, et al, 1992), the pyruvate dehydrogenase complex (Malloch, et al, 1986), the electron transport chain complexes (Almeida, et al, 1995, Bates, et al, 1994, Krebs cycle enzymes (Clark, et al, 1981, Leong and, glutamate dehydrogenase , as well as antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase (Mavelli, et al, 1982). To our knowledge, however, changes in rat brain DLDH expression and activity during postnatal development have not been reported.…”

Section: Introductionmentioning

confidence: 99%

Changes in dihydrolipoamide dehydrogenase expression and activity during postnatal development and aging in the rat brain

Thangthaeng

Forster

2008

Mechanisms of Ageing and Development

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Brain energy metabolism is increased during postnatal development and diminished in neurodegenerative diseases linked to senescence. The objective of this study was to determine if these conditions could involve postnatal or senescence-related shifts in activity or expression of dihydrolipoamide dehydrogenase (DLDH), a key mitochondrial oxidoreductase. Rats ranging from 10 to 60 days of age were used in studies of postnatal development, whereas rats aged 5 or 30 months were used in the aging studies. The expression of DLDH was determined by Western blot analysis using anti-DLDH antibodies and DLDH diaphorase activity was measured by an in-gel activity staining method using nitroblue tetrazolium (NBT)/NADH. Activity of DLDH dehydrogenase was measured as NAD + oxidation of dihydrolipoamide. When these measures were considered in separate groups of 10-, 20-, 30-, or 60-day-old rats, all three showed an increase between 10 and 20 days of age. However, dehydrogenase activity of DLDH showed a further, progressive increase from 20 days to adulthood, in the absence of any further change in DLDH expression or diaphorase activity. No age-related decline in DLDH activity or expression was evident over the period from 5 to 30 months of age. Moreover, aging did not render DLDH more susceptible to oxidative inactivation by mitochondria-generated reactive oxygen species (ROS). Taken together, results of the present study indicate that (1) brain DLDH expression and activity undergo independent postnatal maturational increases; (2) Senescence does not confer any detectable change in the activity of DLDH or its susceptibility to inactivation by mitochondrial oxidative stress.

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Postnatal Development of the Complexes of the Electron Transport Chain in Synaptic Mitochondria from Rat Brain

Cited by 43 publications

References 22 publications

Quantification of the synaptosomal proteome of the rat cerebellum during post-natal development

Quantification of the synaptosomal proteome of the rat cerebellum during post-natal development

Complex I Is Rate-limiting for Oxygen Consumption in the Nerve Terminal

Changes in dihydrolipoamide dehydrogenase expression and activity during postnatal development and aging in the rat brain

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