STUDIES OF THE CONTROL OF MITOCHONDRIAL PROTEIN SYNTHESIS IN TISSUES OF THE RAT.
Item
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Title
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STUDIES OF THE CONTROL OF MITOCHONDRIAL PROTEIN SYNTHESIS IN TISSUES OF THE RAT.
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Identifier
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AAI8203316
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identifier
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8203316
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Creator
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RINEHART, RONALD WAYNE.
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Date
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1981
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Biochemistry
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Abstract
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Investigations were conducted into the mechanisms by which mitochondrial protein synthesis is governed in tissues of the rat. The historical perspectives leading to the current state of understanding of the role of mitochondrial protein synthesis in the overall process of mitochondrial biogenesis are discussed. A particularly useful tool in these investigations was the examination of the effects of streptozotocin-induced diabetes mellitus upon mitochondria from rat skeletal muscle and kidney. The rate of amino acid incorporation in vitro by isolated muscle mitochondria from diabetic animals was decreased by 50-80% from control values. Treatment of diabetic animals with insulin lowered blood glucose levels to control values and restored the rate of muscle mitochondrial protein synthesis in vitro to control levels. The rates of muscle mitochondrial protein synthesis in vitro were decreased by 25% when the animals were fasted for two days. Comparison by dodecyl sulfate polyacrylamide gel electrophoresis of the translation products synthesized by isolated muscle mitochondria from control and diabetic rats revealed a uniform decrease in the synthesis of all polypeptides in the latter. Aurintricarboxylic acid and pactamycin, inhibitors of peptide chain initiation, blocked protein synthesis in vitro by muscle mitochondria to a greater extent in controls than in diabetics, suggesting that diabetic muscle mitochondria are less able to initiate protein synthesis than control muscle mitochondria.;Phenotypic changes observed in diabetic muscle mitochondria included a 36% decrease in the content of cytochrome aa(,3) and a 27% decrease in cytochrome b, both of which contain products of mitochondrial translation. State 3 and uncoupler-stimulated respiration (with glutamate as substrate) were both decreased by about 25% in diabetic mitochondria. By contrast, the specific activities of NADH and succinate dehydrogenases, exclusively products of cytoplasmic translation, were not decreased in muscle mitochondria from diabetic animals; the specific muscle content of mitochondria was also unchanged in the diabetic. These results suggest that the considerable muscular atrophy observed in diabetics may involve decreases in both cytoplasmic and mitochondrial protein synthesis, the latter reflected in profound differences in the respiratory chain.;By contrast with these findings, comparison of kidney mitochondria from control and diabetic rats revealed no real differences in the rates of protein synthesis in vitro, cytochrome content, state 3 respiration, specific activity of succinate dehydrogenase, and the recovery of mitochondria from kidney homogenates. Kidney mitochondria are thus like liver mitochondria in being relatively unaffected by insulin deprivation. The translation product synthesized in vitro by mitochondria from rat kidney, liver, and skeletal muscle are very similar to each other.;The close correlation between the effects of diabetes mellitus upon the rates of total cytoplasmic protein synthesis in vivo and mitochondrial protein synthesis in vitro suggested that, as a lower eukaryotes, mitochondrial protein synthesis may be governed by cytoplasmic translation products. This hypothesis was further investigated by comparing the ability of cytoplasmic post-polysomal supernates from control, diabetic, and cycloheximide treated animals to stimulate protein synthesis in vitro by isolated rat muscle, rat liver, and yeast mitochondria. The results of these experiments indicated some degree of support for this hypothesis. All of these findings are discussed within the context of the current picture of mitochondrial biogenesis.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
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Program
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Biomedical Sciences
