Showing papers on "Mitochondrial biogenesis published in 1989"

Nucleo-mitochondrial interactions in yeast mitochondrial biogenesis.

Abstract: For what once were probably free-living aerobic bacteria, mitochondria show a surprising degree of domestication in terms of their dependence on the genetic system of the cells in which they reside. In most organisms, only a handful of the hundred or so mitochondrial proteins are encoded by mitochondrial DNA (mtDNA). The remainder, including most of the components of the mitochondrion’s own genetic system, are encoded by nuclear genes, which also specify all other enzymes necessary for the synthesis, import, processing and modification of these proteins and associated lipid components. The assembly of a functional mitochondrion is possibly one of the most complex logistic exercises faced by the eukaryotic cell. In a facultative anaerobic organism like the yeast Saccharomyces cerevisiae, which is capable of tailoring the level of mitochondrial biosynthesis to its specific needs in response to its environment, several hundred nuclear genes are likely to be involved in one way or another with mitochondrial biogenesis.

Stimulated Rat Liver Mitochondrial Biogenesis after Partial Hepatectomy

Abstract: In order to elucidate the response of mitochondria to the increase in cellular energy demand after hepatectomy, we have examined the effects of partial hepatectomy and hepatic artery ligation on the energy-transducing system of rat liver mitochondria. Specific content of DNA in the mitochondria increased on the first day after the hepatectomy and reached 150% of the original value. Oxidative phosphorylation capacity of the mitochondria started to increase on the first postoperative day. In contrast, specific enzymic activities, specific cytochrome contents, and subunit contents of the energy-transducing complexes in the isolated mitochondria were significantly increased only from the second postoperative day. The ligation of the hepatic artery did not inhibit the amplification of the mitochondrial function. The immunostain for ubiquinol-cytochrome c oxidoreductase was increased predominantly in the portal area of the hepatic lobules of the hepatectomized rats. These results suggest that enhancement of the mitochondrial oxidative phosphorylation system after hepatectomy is based on the increase of the amount of the complexes in the inner membrane, which is closely related to replication of mitochondrial DNA, and that the blood supply from the hepatic artery is not an important factor in the mitochondrial amplification in rats.

Thyroid hormone and not growth hormone is the principle regulator of mammalian mitochondrial biogenesis.

Abstract: T3 and GH have been implicated in the regulation of mitochondrial biogenesis. Since thyroid hormone promotes the synthesis of growth hormone, its control of human mitochondrial biogenesis could arise through a permissive action on GH biosynthesis. This was studied in hypophysectomized rats treated with T3 and/or human GH by the continuous infusion of hormone for 6 days from mini-infusion pumps implanted sc. Increases in mitochondrial respiration, enzyme activities, and protein synthesis were found in isolated liver mitochondria from rats receiving T3. In contrast, GH alone had no effect, nor did it increase the response to T3. Since it has been argued that mitochondrial biogenesis results from a direct interaction (binding) of GH with mitochondria, GH-specific binding sites were measured with 125I-bGH, a specific somatogenic receptor ligand, in isolated mitochondrial membranes in vitro. In addition, the intracellular endocytic uptake of 125I-bGH injected in vivo was compared in purified subcellular membrane fractions and mitochondria. No evidence in favour of specific GH interaction on mitochondrial membranes was found by either test. It is concluded that T3 exerts a direct, rather than permissive, effect on mitochondrial biogenesis, and that high affinity binding sites for GH are not present in rat liver mitochondria.

Content of Mitochondrial DNA and of Three Mitochondrial RNAs in Developing and Adult Rat Cerebellum

Abstract: The content of DNA and of 16S rRNA and of two mRNAs, i.e., the mRNA for the cytochrome c oxidase subunit I and the mRNA for one subunit of the NADH dehydrogenase (ND4), in free (nonsynaptic) mitochondria of developing and adult rat cerebellum has been determined. During postnatal development, DNA content of free (nonsynaptic) mitochondria increases 10 times from 1 to 30 days of age whereas, in adult rats, it is about 60% compared to that found in 30-day-old rats. The total content of each RNA species studied also increases during development. However, when the content of each RNA is expressed per mtDNA molecule, rRNAs and mRNAs behave differently: 16S rRNA level does not change during development and it is not significantly different from that of the adult rat, whereas the level of mRNAs is higher during development than in the adult rat and changes with age. These results are discussed in light of mitochondrial biogenesis in rat cerebellum during development and of the regulation of the mitochondrial DNA transcription process.

Thyroid hormone regulation of nuclear-encoded mitochondrial inner membrane polypeptides of the liver.

Abstract: The effects of thyroid hormone on nuclear-encoded mitochondrial inner membrane proteins was investigated by in vitro translation of the endogenous mRNA present in a postmitochondrial fraction from the livers of rats treated in vivo with hormone. The levels of the mRNAs were estimated by quantitative immunoabsorption of the translation mixture. Total protein synthesis was increased 2.6-fold after 4 days of in vivo hormone treatment, but only 10–15% of the polypeptides were dramatically altered (> 5-fold). Among the most highly elevated were cytochrome c1 (> 10-fold increase) and the Rieske iron-sulfur protein of the cytochrome bc1 complex. Other inner membrane proteins (core protein 1, β subunit of F1 ATPase, subunit IV of cytochrome oxidase, 3-hydroxybutyrate dehydrogenase) and non-mitochondrial proteins (rat serum albumin, β2-microglobulin) were not altered significantly by hormone treatment. Cytochrome c1 and the Rieske protein increased after 12 h of hormone treatment, a relatively early response in mammalian mitochondrial biogenesis. The possible significance of this response for the regulation of mitochondrial synthesis and assembly is discussed.

Identification and metabolic characterization of the Zea mays mitochondrial homolog of the Escherichia coli groEL protein.

Abstract: We have characterized an abundant mitochondrial protein from Zea mays and have shown it to be structurally and metabolically indistinguishable from a previously described Tetrahymena thermophila and Saccharomyces cerevisiae mitochondrial protein, referred to as hsp60, which is homologous to the groEL protein of Escherichia coli. This Z. mays protein, which we also refer to as hsp60, was found to be antigenically quite distinct from the chloroplast Rubisco-binding protein, another groEL homolog. Using an antiserum directed against the T. thermophila hsp60, we determined that the relative concentration of Z. mays hsp60 was two to four times higher in mitochondria isolated from tissues of early developmental stages than that found in mitochondria isolated from more adult tissues. Given the known and suggested roles of the other members of the groEL family of proteins, our results suggest that the Z. mays hsp60 may play an important role in mitochondrial biogenesis during early plant development.

Mitochondrial Biogenesis During the Activation of Lymphocytes by Mitogens: The Immunosuppressive Action of Tetracyclines

Abstract: The role of mitochondrial biogenesis and function during mitogenic stimulation of rat thymocytes was investigated. The results show that mitochondrial biogenesis is required to provide the ATP for the energy-requiring processes occurring during blastogenesis. Impairment of mitochondrial biogenesis by inhibition of mitochondrial protein synthesis inhibits blast transformation. Since the tetracyclines impair mitochondrial protein synthesis, the results offer an explanation for the well-known immunosuppressive effects of these antibiotics.

Ascaris suum: A Useful Model for Anaerobic Mitochondrial Metabolism and the Aerobic- anaerobic Transition in Developing Parasitic Helminths

Abstract: The developmental cycle of Ascaris suum involves a transition from free-living stages, that use aerobic energy generating pathways, to adult worms, where pathways are maximally adapted to anaerobic energy generation. Mitochondria from A. suum provide an excellent model for studies of anaerobic metabolism and mitochondrial biogenesis. Adult worm body wall muscle has been used as a single tissue source for large scale isolation of anaerobic mitochondria for studies on regulation of some of the key soluble enzymes and comparison with counterparts in aerobic tissues. The basic catalytic mechanism of the ascarid pyruvate dehydrogenase complex is, for example, similar to its aerobic counterpart, its regulation however exhibits a number of unique features many of which can be directly related to its anaerobic environment. Another example is provided by the pathways of branched chain fatty acid synthesis in Ascaris, which characteristically involve the reversal of β-oxidation operative in mammalian mitochondria. Electron transfer is NADH dependent and the enzyme methyl branched-chain acyl CoA dehydrogenase differs in its regulatory properties in accord with its physiological function as a reductase. Key regulatory proteins of adult mitochondria have been purified to homogeneity and recent advances include the preparation of polyclonal antibodies. These can provide sensitive assays for the molecular events governing mitochondrial biogenesis during transition from aerobic to anaerobic energy generation during the moult from L3 to L4. This ascarid system is ideally suited to investigate a number of important questions about the aerobicanaerobic transition present in many different helminths.

Antitumor Effect of Drugs Interfering with Mitochondrial Biogenesis

Abstract: Most of the rapidly growing tumors have a high capacity of aerobic glycolysis. Warburg’s hypothesis explaining this phenomenon by an impaired respiratory capacity of tumor cells attracted much attention in the past. The attempts to define the supposed defect(s) in oxidative metabolism of cancer cells were unsuccessful. Tumor mitochondria differ often very significantly from the organelles of the tissue of origin [review in 1]. These differences probably do not account for the altered, relative contributions of oxidative phosphorylation and glycolysis to the total cellular energy production in rapidly growing tumors. More relevant to the altered pattern of the tumor energy metabolism seems to be the diminished content of mitochondria in tumor cells, especially in the cells of rapidly growing tumors [review in 1]. In spite of their low content the organelles are indispensable to tumor energetics; even in the highly glycolyzing tumors oxidative phosphorylation covers no less than 50% of the energy demands of the cells [2]. Lower capacity of oxidative phosphorylation accompanying the reduced content of mitochondria in tumor cells has been employed in developing a new approach to cancer chemotherapy by using drugs interfering with the formation of functional mitochondria [3–5]. This communication deals with the mechanism by which inhibitors of mitochondrial biogenesis exert their antitumor effect.