Showing papers on "Mitochondrial biogenesis published in 1990"
TL;DR: Immunoprecipitation of radiolabeled subunits of these enzymes showed that the initiation of mitochondrial biogenetic activities, including de novo synthesis of nuclear- and mitochondrial-encoded enzyme subunit peptides, was strongly induced after 6 hours of embryo germination.
Abstract: Function of the cyanide-sensitive mitochondrial electron transport system was required for germination of the Zea mays embryo. Respiration of the standard electron transport system (rather than the alternate oxidase) began immediately upon initiation of imbibition. This respiration depended upon cytochrome c oxidase and ATPase that were conserved in an active form in the quiescent embryo rather than upon newly synthesized or assembled enzyme complexes. Immunoprecipitation of radiolabeled subunits of these enzymes showed that the initiation of mitochondrial biogenetic activities, including de novo synthesis of nuclear- and mitochondrial-encoded enzyme subunit peptides, was strongly induced after 6 hours of embryo germination. Undetectable or very low levels of transcripts for subunits 1 and 2 of the F(1)-ATPase and subunit 2 of cytochrome c oxidase were present in the quiescent embryo; these transcripts accumulated rapidly between 6 and 12 hours of germination and their translation products were rapidly synthesized between 6 and 24 hours. An exception was the gene for subunit 9 of the ATPase; transcripts of this mitochondrial gene were abundant in the dry embryo and rapidly accumulated further upon initiation of imbibition; they were translated actively during the first 6 hours. We isolated and sequenced a near full-length cDNA for subunit 2 (beta) of the F(1)-ATPase, and we compared the deduced protein sequence with related sequences of other organisms.
100 citations
TL;DR: Analysis of proteins synthesized in the presence of emetine showed that the synthesis of several mitochondrial translation products, including cytochrome b, was reduced after treatment with interferon, revealing a novel effect of interfer on cellular physiology.
Abstract: As an approach to identifying genes involved in physiological actions of interferons we used differential probes to screen a cDNA library from mouse L-929 cells treated with interferon alpha/beta. We identified two negatively regulated mRNA species which have been examined by analysis of the corresponding mRNAs and by DNA sequencing. Comparison with the GenBank database showed that these cDNA clones corresponded to mitochondrially encoded genes for cytochrome b and subunit I of cytochrome c oxidase. A further cDNA encompassing three mitochondrial genes was used as a probe to show that a third mRNA, NADH dehydrogenase subunit 5, was also down-regulated by interferon while a fourth, NADH dehydrogenase subunit 6, was unaffected. Expression of cytochrome b was also inhibited in mouse NIH 3T3 cells treated with interferon alpha/beta and in human Daudi lymphoblastoid cells treated with interferon alpha. The ability of interferon to reduce mitochondrial mRNA levels could be blocked by cycloheximide suggesting that these effects are mediated by an interferon-responsive nuclear gene which encodes a product capable of regulating mitochondrial gene expression. Analysis of proteins synthesized in the presence of emetine, a specific inhibitor of cytoplasmic translation, showed that the synthesis of several mitochondrial translation products, including cytochrome b, was reduced after treatment with interferon. Our results reveal a novel effect of interferon on cellular physiology which could have important consequences for understanding the effects of interferons as well as suggesting new mechanisms for the regulation of mitochondrial biogenesis and function.
88 citations
TL;DR: Thyroid hormone exerts two types of effect on mitochondria: a rapid activation of respiration which takes place within minutes after hormone injection, and is preserved in isolated mitochondria, and a response which occurs after 1 to several days of injection and leads to mitochondrial biogenesis and increases in mitochondria mass.
58 citations
TL;DR: Comparison studies with NAO and rhodamine 123 prove that acridine orange-derivative uptake is independent of transmembrane mitochondrial potential, a property allowing its utilization for the assessment of mitochondrial membrane mass modifications under various physiological states.
58 citations
TL;DR: The results strongly suggest that the variations in size, distribution and density of mitochondria relate to the particular energetic requirements of the different cell types during the first half of oogenesis, and that the mt RNA density is under extramitochondrial control mechanisms.
24 citations
TL;DR: The article summarizes the response of mitochondria and plastids in various organisms to drugs and environmental xenobiotics as well as the possible consequences of such interaction.
Abstract: Bacterial ancestry of mitochondria and plastids is now generally accepted. Both organelles contain their own DNA and transcription-translation apparatus of a prokaryotic type. Due to this fact these systems carry bacteria-like properties. Thus organellar DNA and ribosomes are essentially different from nuclear DNA and cytoplasmic ribosomes in physical as well as in functional respects. Due to the bacterial character of both types of organelles they are susceptible to various antibacterial chemicals. Inhibitors of bacterial protein synthesis inhibit mitochondrial (plastidial) biogenesis. Therefore the cellular content of mitochondria (plastids)-made proteins decreases during cytoplasmic turnover or cell division in the presence of these drugs. Such drug activity consequently leads to a reduced capacity for oxidative phosphorylation or photosynthesis. Organellar genomes are less stable and more sensitive to mutagenesis as compared to nuclear genome. It means also that genotoxic agents induce various disorders of mitochondrial (plastidial) functions. Impairments in the respiratory chain are associated with structural as well as functional abnormalities of mitochondria. These are clinically expressed mostly in tissues with a high demand for ATP: brain, heart, skeletal muscle, and retina. On the other hand, some antibacterial inhibitors of mitochondrial biogenesis (e.g., tetracyclines) inhibit selectively tumor cell proliferation. Therefore they may be considered for use in anticancer therapy.
The article summarizes the response of mitochondria and plastids in various organisms to drugs and environmental xenobiotics. Various model organisms suitable for detection of xenobiotic effect on mitochondria (plastids) are presented as well as the possible consequences of such interaction.
22 citations
TL;DR: Whereas RCR was a useful predictor of mitochondrial translation rates, it did not account for the effects of insulin on mitochondrial translation.
Abstract: The rates of synthesis of mitochondrial proteins by both the cytoplasmic and mitochondrial protein synthetic systems, as well as parameters of respiration, were measured and compared in mitochondria isolated from fresh, control perfused, and insulin-perfused rat hearts. The respiratory control ratio (RCR) in mitochondria from fresh hearts was 8.1 +/- 0.4 and decreased to 6.0 +/- 0.2 (P less than 0.001 vs. fresh) in mitochondria from control perfused hearts and to 6.7 +/- 0.2 (P less than 0.005 vs. fresh and P less than 0.02 vs. control perfused) for mitochondria from hearts perfused in the presence of insulin. A positive correlation between the RCR and the rate of mitochondrial translation was demonstrated in mitochondria from fresh hearts. In mitochondria isolated from control perfused hearts, the rate of protein synthesis decreased to 84 +/- 3% of the fresh rate after 30 min of perfusion and fell further to 64 +/- 3% after 3 h of perfusion. The inclusion of insulin in the perfusion buffer stimulated mitochondrial protein synthesis 1.2-fold by 1 h (P less than 0.005) and 1.34-fold by 3 h of perfusion (P less than 0.001). The addition of insulin to 1-h control perfused hearts shifted the rate of mitochondrial protein synthesis from the control level to the insulin-perfused level within 30 min of additional perfusion, whereas 1 h was required to shift the RCR values of these mitochondria from control levels to insulin-perfused levels. Thus, whereas RCR was a useful predictor of mitochondrial translation rates, it did not account for the effects of insulin on mitochondrial translation.(ABSTRACT TRUNCATED AT 250 WORDS)
19 citations
TL;DR: It was demonstrated that optimal isolated heart mitochondrial protein synthesis required the presence of an oxidizable substrate, indicating for the first time that mitochondrial translation, like its cytoplasmic counterpart is regulated by energy charge.
Abstract: Although much is now known with regard to the processes of mammalian mitochondrial gene expression, relatively little is known concerning the quantitative regulation of this pathway in response to hormones or other physiological stimuli. In this paper the potential coupling of mitochondrial metabolism to mitochondrial protein synthesis was investigated and the concentration of nucleotides and substrates for optimal translation in isolated rat heart mitochondria was determined. It was demonstrated that optimal isolated heart mitochondrial protein synthesis required the presence of an oxidizable substrate. Of the substrates tested, glutamate (20 mM) supported translation best followed by malate, succinate, and alpha-ketoglutarate, whereas pyruvate supported synthesis poorly. Unlike other recent mammalian mitochondrial systems, the presence of an oxidizable substrate was required for translation even in the presence of medium ATP and an exogenous energy-generating system. Mitochondrial translation also required the presence of adenine nucleotide that could be added as ADP or ATP; however, ATP added above 0.5 mM became progressively inhibitory. As a result, synthesis was supported significantly better by ATP synthesized by the system from added ADP, than by ATP added directly to the system. However, if the phosphorylation of ADP was prevented by limiting the phosphate concentration, ADP itself strongly inhibited mitochondrial protein synthesis. This inhibition appeared to be closely related to the energy charge of the system rather than to absolute levels of ADP, indicating for the first time that mitochondrial translation, like its cytoplasmic counterpart is regulated by energy charge. Last, this system did not require the inhibition of guanine nucleotide or exogenous energy-generating systems.(ABSTRACT TRUNCATED AT 250 WORDS)
13 citations
TL;DR: Rates of mitochondrial protein synthesis were dramatically stimulated by T3-thyroxine injection, and the decline in stimulation of cytoplasmic synthesis of mitochondrial proteins was significantly steeper, falling to 119% of vehicle control.
Abstract: The goal of this paper was to determine the effects of 3,5,3'-triiodothyronine (T3)-thyroxine-induced cardiac hypertrophy on the rates of synthesis of mitochondrial proteins by both the cytoplasmic...
12 citations
TL;DR: Studies of bioenergetic modifications in a TTR1 single-nuclear mutant, isolated as resistant to triethyltin, an inhibitor of mitochondrial ATPase, and effective in cAMP-dependent protein phosphorylation, found that ATP synthesis rate in mutant cells in both the prestationary and stationary phase of growth appeared increased in comparison to wild-type cells.
Abstract: This paper reports studies of bioenergetic modifications in a TTR1 single-nuclear mutant, isolated as resistant to triethyltin, an inhibitor of mitochondrial ATPase, and effective in cAMP-dependent protein phosphorylation. This mutant appears to have lost the wildtype cell ability to respond to a decrease of oxygen concentration in the growth medium by a decrease of cytochrome concentration in the cell. ATP synthesis rate in mutant cells in both the prestationary and stationary phase of growth appeared increased in comparison to wild-type cells, as too was respiration rate. A comparative study of mitochondria extracted from wild-type and from TTR1 mutant cells showed an increase in respiration rate, an increase in ATP synthesis rate, and an increase in TPP+ uptake in mutant mitochondria. The specific ATPase activity, as well as its sensitivity to TET, appears to be similar for mitochondria extracted from both strains. It was proposed that the modification of mitochondrial biogenesis in the TTR1 mutant may be due to a response of the cell to an increase in ATP hydrolysis caused by the mutation. It is also possible that the modification in cAMP-dependent protein kinase regulation which appeared to occur in this mutant affects protein(s) involved in mitochondrial biogenesis.
12 citations
TL;DR: Supporting evidence for conversion over biased transmission is shown by preferential recovery of a nonparental genome in the progeny of a heterozygous cross in which both parental molecules can be identified by size polymorphisms.
Abstract: Saccharomyces cerevisiae mitochondrial DNA deletion mutants have been used to examine whether base-biased intergenic regions of the genome influence mitochondrial biogenesis. One strain (delta 5.0) lacks a 5-kilobase (kb) segment extending from the proline tRNA gene to the small rRNA gene that includes ori1, while a second strain (delta 3.7) is missing a 3.7-kb region between the genes for ATPase subunit 6 and glutamic acid tRNA that encompasses ori7 plus ori2. Growth of these strains on both fermentable and nonfermentable substrates does not differ from growth of the wild-type strain, indicating that the deletable regions of the genome do not play a direct role in the expression of mitochondrial genes. Examination of whether the 5- or 3.7-kb regions influence mitochondrial DNA transmission was undertaken by crossing strains and examining mitochondrial genotypes in zygotic colonies. In a cross between strain delta 5.0, harboring three active ori elements (ori2, ori3, and ori5), and strain delta 3.7, containing only two active ori elements (ori3 and ori5), there is a preferential recovery of the genome containing two active ori elements (37% of progeny) over that containing three active elements (20%). This unexpected result, suggesting that active ori elements do not influence transmission of respiratory-competent genomes, is interpreted to reflect a preferential conversion of the delta 5.0 genome to the wild type (41% of progeny). Supporting evidence for conversion over biased transmission is shown by preferential recovery of a nonparental genome in the progeny of a heterozygous cross in which both parental molecules can be identified by size polymorphisms.
TL;DR: Mitochondrial ATPase dysfunction does not appear to be the inciting factor in the proliferation of mitochondria seen in oxyphil cell metaplasia and future studies should consider other possibilities.
01 Jan 1990
TL;DR: There is a preferential recovery of the genome containing twoactive onielements over that containing threeactive elements, suggesting thatactive onIElements don't influence transmission of respiratory-competent genes.
Abstract: Saccharomyces cerevisiae mitochondrial DNA deletion mutantshavebeenusedtoexamine whether base-biased intergenic regions ofthegenome influence mitochondrial biogenesis. Onestrain (A5.0) lacks a 5-kilobase (kb) segment extending fromtheproline tRNAgenetothesmall rRNAgenethatincludes oril, while a second strain (A3.7) ismissing a 3.7-kb region between thegenesforATPasesubunit 6andglutamic acid tRNAthat encompassesori7plusori2. Growthofthese strains on bothfermentable andnonfermentable substrates doesnotdiffer fromgrowth ofthewild-type strain, indicating thatthedeletable regions ofthe genome donotplay a direct role intheexpression ofmitochondrial genes.Examination ofwhether the5-or 3.7-kb regions influence mitochondrial DNA transmission was undertaken bycrossing strains andexamining mitochondrial genotypes inzygotic colonies. Ina crossbetween strain A5.0, harboring three active orielements (ori2, ori3, andoriS), andstrain A3.7,containing onlytwoactive onielements (ori3 andoriS), there isa preferential recoveryofthegenome containing twoactive onielements (37%ofprogeny) overthatcontaining threeactive elements (20%). Thisunexpected result, suggesting thatactive onielements donotinfluence transmission ofrespiratory-competent
TL;DR: Subcellular fractions isolated from livers of 19-day-old chicken embryos were analyzed in order to assess whether liver mitochondria contained glycosylated proteins or had mannosyl- or sialyl-transferases that could transfer sugars to mitochondrial macromolecules.
Journal Article•
TL;DR: Two carbon catabolite repression mutants of S. cerevisiae display hyper-repression of cytochrome aa3 and of certain mitochondrial enzymes but not of others, indicating the existence of separate control sites for the different genes involved in the mitochondrial biogenesis.
Abstract: Two carbon catabolite repression mutants of S. cerevisiae were isolated and characterized. In spite of the selection procedure (red colonies after tetrazolium overlay at high glucose concentration) the mutants exhibited a respiration which was as repressed as that of the parental strain or even more repressed. When grown at high glucose concentration the mutants display hyper-repression of cytochrome aa3 and of certain mitochondrial enzymes (L- and D-lactate dehydrogenases) but not of others (malate dehydrogenase, succinate dehydrogenase), indicating the existence of separate control sites for the different genes involved in the mitochondrial biogenesis. The data obtained pointed out that the same mutation affects both repression and derepression. In addition, the mutation(s) give rise to the complete derepression of the cytoplasmic enzyme NAD-glutamate dehydrogenase at 10% glucose whereas the enzyme is normally repressed at 3% glucose. The results of the genetic analysis indicate the mitochondrial nature of the mutation(s).
TL;DR: In vitro transcription in isolated nuclei has shown a 4-fold stimulation in the synthesis of Iso-1-cytochrome C messengers in repressed but hemin-treated and derepressed cells compared to the repressed cells.
Abstract: Exogenous addition of hemin to glucose-repressed cells ofSaccharomyces cerevisiae restores the level of Iso-1-cytochrome C messengers to that observed in derepressed cells.In vitro transcription in isolated nuclei has shown a 4-fold stimulation in the synthesis of Iso-1-cytochrome C messengers in repressed but hemin-treated and derepressed cells compared to the repressed cells. Studies onin vitro transport of RNA from isolated nuclei have revealed that there is a 50% drop in the transport of total RNA from nuclei isolated from repressed but hemin-treated and derepressed cells when compared with the nuclei from repressed cells. However, under these conditions, there is an enhanced transport of translatable RNA. Hybridization analysis of the transported RNA using Iso-1-cytochrome C gene-specific probe has shown that there is preferential transport of Iso-1-cytochrome C messengers in repressed but hemin treated and derepressed cells.