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At least 19 recordsLinked to original sources
PubMed1996

Iron metabolism-related genes and mitochondrial genes are induced during involution of mouse mammary gland.

To understand molecular mechanisms of mammary gland involution, several clones were isolated after the primary differential screening of a total 40,000 pfu of involution-specific cDNA library, and further characterized. The partial sequences and Northern analysis revealed that iron metabolism-related genes and mitochondrial genes were induced during mammary gland involution. The expression of the lactoferrin gene was induced at involution days 1, 2, and 3. The expression of ferritin heavy chain gene was induced at involution days 1, 2, 3 and 4. Cytochrome oxidase subunit 1 and cytochrome oxidase subunit 2 genes were induced at involution days 4 and 7. The expression of cytochrome b gene was induced at involution day 7. These results imply that iron metabolism and mitochondrial function may be altered during mammary gland involution.

Animals↗
PubMed2005

Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis.

Although several genes involved in mitochondrial function are direct Myc targets, the role of Myc in mitochondrial biogenesis has not been directly established. We determined the effects of ectopic Myc expression or the loss of Myc on mitochondrial biogenesis. Induction of Myc in P493-6 cells resulted in increased oxygen consumption and mitochondrial mass and function. Conversely, compared to wild-type Myc fibroblasts, Myc null rat fibroblasts have diminished mitochondrial mass and decreased number of normal mitochondria. Reconstitution of Myc expression in Myc null fibroblasts partially restored mitochondrial mass and function and normal-appearing mitochondria. Concordantly, we also observed in primary hepatocytes that acute deletion of floxed murine Myc by Cre recombinase resulted in diminished mitochondrial mass in primary hepatocytes. Our microarray analysis of genes responsive to Myc in human P493-6 B lymphocytes supports a role for Myc in mitochondrial biogenesis, since genes involved in mitochondrial structure and function are overrepresented among the Myc-induced genes. In addition to the known direct binding of Myc to many genes involved in mitochondrial structure and function, we found that Myc binds the TFAM gene, which encodes a key transcriptional regulator and mitochondrial DNA replication factor, both in P493-6 lymphocytes with high ectopic MYC expression and in serum-stimulated primary human 2091 fibroblasts with induced endogenous MYC. These observations support a pivotal role for Myc in regulating mitochondrial biogenesis.

Animals↗
PubMed1991

Existence of common homologous elements in the transcriptional regulatory regions of human nuclear genes and mitochondrial gene for the oxidative phosphorylation system.

Our previous study indicated that nuclear protein factors of HeLa cells specifically bind to three nuclear Mt elements, Mt1, Mt3, and Mt4, located in the 5'-flanking regions of the human nuclear genes for cytochrome c1 and for ubiquinone-binding protein, both of which are subunits of mitochondrial cytochrome bc1 complex (Suzuki, H., Hosokawa, Y., Toda, H., Nishikimi, M., and Ozawa, T. (1990) J. Biol. Chem. 265, 8159-8163). In this study, we examined whether the same nuclear factors could recognize a set of the Mt3 and Mt4 elements that were found in the displacement loop and the promoter region of mammalian mitochondrial genomes. Gel retardation experiments disclosed that the same nuclear protein factors specifically bind to those Mt elements in the human mitochondrial genome as well as to the nuclear Mt3 and Mt4 elements of the two genes, and that the coexistence of both the elements is required for the efficient binding. The nuclear protein factors which recognize the Mt elements located in the regulatory regions of the nuclear and mitochondrial genes may play an important role in coordinate expression of the two physically separated genes during mitochondrial biogenesis.

Base Sequence↗
PubMed1999

Conversion of a reporter gene for mitochondrial gene expression using iterative mega-prime PCR.

Mammalian mitochondria possess their own multicopy genome, mtDNA. Although much is known about mtDNA replication and transcription, our knowledge of the mechanisms governing mt-RNA processing, stability and translation remains rudimentary. We have taken a step towards addressing these issues by altering the luciferase reporter gene to accommodate the variation in mitochondrial codon recognition. 19 essential substitutions have been generated by an iterative mega-primer PCR technique. To mimic mt-mRNA species and to optimise intramitochondrial translation, further engineering has produced a template which, when transcribed in vitro, generates an RNA species with only two nucleotides upstream from the initiation codon, an absence of a 3' untranslated region and a polyadenylated tail of 40 residues. It is intended that mt-luciferase (mt-luc) RNA will be an excellent reporter for revealing cis-acting elements essential for in organello RNA processing, maturation and expression. Additionally, the mt-luc gene can be readily incorporated into any novel mitochondrial transducing vectors to assess intra-organellar transcription and translation.

DNA Primers↗
PubMed1996

Nuclear inheritance of a gene affecting mitochondrial gene expression.

Due to a deficiency in mitochondrial protein synthesis, Chinese hamster lung (CHL) cell mutant Gal- 32 does not grow in galactose or fructose. This report examines the nuclear or cytoplasmic inheritance of this single, recessive mutation. In a control experiment, fusion of Gal+TGSTK- cells with Gal- 32TGRTK+ cells resulted in tetraploid hybrids (as verified by karyotyping) that were selected in hypoxanthine/aminopterin/thymidine medium. The majority (2/3) of the control hybrids grew in galactose as expected since Gal+ is dominant over Gal-. Fusion of Rhodamine 6-G treated Gal+TGSTK- cells with Gal- 32TGRTK+ cells resulted in Rhodamine 6-G-tetraploid hybrids that were selected in hypoxanthine/aminopterin/thymidine medium. The majority (7/12) of the Rhodamine 6-G-hybrids grew in galactose as expected for a nuclearly encoded gene considering that Rhodamine 6-G interferes with transmission of mtDNA but not nuclear DNA. Therefore, these results are compelling in their demonstration of the nuclear origin of the Gal- 32 mutation.

Animals↗
PubMed1984

A nuclear mutation that post-transcriptionally blocks accumulation of a yeast mitochondrial gene product can be suppressed by a mitochondrial gene rearrangement.

The nuclear amber mutation, pet494-1, specifically blocks the accumulation of the product of the mitochondrial gene oxi2, cytochrome oxidase subunit III. The pet494-1 mutation does not prevent transcription of the mitochondrial gene since RNA--gel blot hybridizations showed that mutant cells contain normal amounts of an oxi2 transcript, indistinguishable in size from wild-type. A mitochondrial mutation that partially suppresses the nuclear mutation was isolated. The "mitochondrial revertant" behaved as though it contained two different mitochondrial DNAs: one rho+, the other rho-. The suppressor mutation is carried on the rho- mitochondrial DNA and is apparently the result of a gene fusion between oxi2 and another mitochondrial gene, oxi3. This gene rearrangement replaced the normal 5'-non-translated sequence of oxi2 with a portion of the open reading frame of the second intron of oxi3. Novel transcripts of the rearranged gene, containing oxi3 sequences upstream from oxi2 were detected in the mitochondrial revertant. The strain accumulated an electrophoretically variant form of cytochrome oxidase subunit III, probably translated from a new initiation codon. The data are consistent with models in which the PET494 protein acts within the mitochondria to specifically promote the translation of the oxi2 messenger RNA.

DNA, Mitochondrial↗
PubMed2002

Punctuated evolution of mitochondrial gene content: high and variable rates of mitochondrial gene loss and transfer to the nucleus during angiosperm evolution.

To study the tempo and pattern of mitochondrial gene loss in plants, DNAs from 280 genera of flowering plants were surveyed for the presence or absence of 40 mitochondrial protein genes by Southern blot hybridization. All 14 ribosomal protein genes and both sdh genes have been lost from the mitochondrial genome many times (6 to 42) during angiosperm evolution, whereas only two losses were detected among the other 24 genes. The gene losses have a very patchy phylogenetic distribution, with periods of stasis followed by bursts of loss in certain lineages. Most of the oldest groups of angiosperms are still mired in a prolonged stasis in mitochondrial gene content, containing nearly the same set of genes as their algal ancestors more than a billion years ago. In sharp contrast, other plants have rapidly lost many or all of their 16 mitochondrial ribosomal protein and sdh genes, thereby converging on a reduced gene content more like that of an animal or fungus than a typical plant. In these and many lineages with more modest numbers of losses, the rate of ribosomal protein and sdh gene loss exceeds, sometimes greatly, the rate of mitochondrial synonymous substitutions. Most of these mitochondrial gene losses are probably the consequence of gene transfer to the nucleus; thus, rates of functional gene transfer also may vary dramatically in angiosperms.

Base Sequence↗
PubMed1992

Differential expression of the mouse mitochondrial genes and the mitochondrial RNA-processing endoribonuclease RNA by androgens.

Using subtractive hybridization to identify genes that are androgen regulated in the mouse epididymis, a number of cDNAs were identified that represented mitochondrial genes including cytochrome oxidase c subunits I, II, and III, cytochrome b, NADH dehydrogenase subunit 5, a region of the displacement loop, and the 16S rRNA. Northern blot analysis of RNA from intact, castrate, or testosterone-replaced epididymides confirmed that these mitochondrial mRNAs as well as the rRNA were androgen regulated with a 2- to 5-fold reduction in expression observed after 4 weeks castration with partial to full recovery to precastrate levels upon 4 weeks of testosterone replacement. In contrast to the mitochondrial genes, the expression of the RNA component of the mitochondrial RNA-processing endoribonuclease (RNAase MRP), a nuclear factor which is thought to be involved in the regulation of mitochondrial DNA synthesis, increased in the epididymis upon castration and then returned to precastrate levels after testosterone replacement. An examination of other androgen-responsive tissues showed that mitochondrial gene expression was also regulated by androgens in the kidney. The RNAase MRP RNA levels, however, showed an increase after castration only in the reproductive tissues (epididymis, vas deferens, and seminal vesicle) and not in the kidney. No correlative increase in mitochondrial DNA levels was observed for any of the tissues. Finally, an analysis of various mouse tissues as well as the different regions of the epididymis revealed large differences in mitochondrial mRNA levels. While for most tissues the mRNA levels correlated with the mitochondrial DNA content, the levels of the RNAase MRP RNA did not. Taken together, these findings not only show the large variations in mitochondrial gene expression between tissues but also demonstrate that the expression of mitochondrial genes and ultimately mitochondrial function are androgen regulated in the epididymis and kidney.

Animals↗
PubMed1987

Developmental regulation of trypanosome mitochondrial gene expression.

Mitochondrial respiratory activities in the protozoan parasite Trypanosoma brucei are developmentally regulated. The trypanosomes in the mammalian bloodstream derive ATP entirely from glycolysis. The trypanosomes found in the midgut of the insect vector or in culture at 26 degrees C have fully functional mitochondria with cytochrome-mediated respiration. In this paper, we show that the steady state levels of the 9 S and 12 S mitochondrial ribosomal RNAs (rRNAs) are 30-fold lower in an early developmental stage in the mammal, the slender forms, relative to the levels in the stumpy trypanosomes, a later developmental stage in the mammalian infection. Transcripts from three other mitochondrial genes, cytochrome b and subunits I and II of cytochrome oxidase, are undetectable in the slender trypanosomes and increase in the stumpy trypanosomes to levels approaching those in trypanosomes from 26 degrees C cultures. Transcription of other mitochondrial genes, including NADH-dehydrogenase subunit 5, is unregulated during trypanosome development. These results show that the level of some mitochondrial transcripts is developmentally regulated in bloodstream trypanosomes and suggest that the stumpy bloodstream trypanosomes accumulate mitochondrial transcripts prior to development of a functional mitochondrion. These results also show that the developmental activation of mitochondrial activities at 26 degrees C is not controlled at the level of mitochondrial transcription.

Animals↗
PubMed1997

Interferons suppress mitochondrial gene transcription by depleting mitochondrial transcription factor A (mtTFA).

Mitochondrial gene transcription activity in organello was suppressed after culturing HeLa cells with 1000 U/ml of interferon-alpha (IFN-alpha) or IFN-gamma for 18 h. The suppression was associated with reduced levels of mitochondrial gene transcripts. Northern blot analysis of HeLa cell RNA showed marked reduction of the mRNA encoding for mitochondrial transcription factor A (mtTFA). Immunoblotting with antiserum directed against recombinant mtTFA showed a reduced level of the protein as well. Consistently, gel-retardation assay of mitochondrial extract showed reduced level of functional mtTFA, which is known to bind to both heavy and light strand promoters of bidirectionally transcribed mitochondrial DNA. We suggest that depletion of mtTFA is a pathway through which IFNs depress the mitochondrial respiration.

DNA-Binding Proteins↗
PubMed1983

Biogenesis of mitochondria: the mitochondrial gene (aap1) coding for mitochondrial ATPase subunit 8 in Saccharomyces cerevisiae.

A mitochondrial gene (denoted aap1) in Saccharomyces cerevisiae has been characterized by nucleotide sequence analysis of a region of mtDNA between the oxi3 and oli2 genes. The reading frame of the aap1 gene specifies a hydrophobic polypeptide containing 48 amino acids. The functional nature of this reading frame was established by sequence analysis of a series of mit- mutants and revertants. Evidence is presented that the aap1 gene codes for a mitochondrially synthesized polypeptide associated with the mitochondrial ATPase complex. This polypeptide (denoted subunit 8) is a proteolipid whose size has been previously assumed to be 10 kilodaltons based on its mobility on SDS-polyacrylamide gels, but the sequence of the aap1 gene predicts a molecular weight of 5,815 for this protein.

Adenosine Triphosphatases↗
PubMed2005

Multiple promoters are a common feature of mitochondrial genes in Arabidopsis.

Mitochondrial genes in the plant Arabidopsis thaliana are transcribed by two phage-type RNA polymerases encoded in the nucleus. Little is known about cis-elements that are recognized by these enzymes and mediate the transcription of the Arabidopsis mitochondrial genome. Here, 30 transcription initiation sites of 12 mitochondrial genes and gene clusters have been determined using 5'-RACE and ribonuclease protection analysis of primary transcripts labelled in vitro by guanylyltransferase. A total of 9 out of 12 genes were found to possess multiple promoters, revealing for the first time that multiple promoters are a common feature of mitochondrial genes in a dicotyledonous plant. No differences in promoter utilization were observed between leaves and flowers, suggesting that promoter multiplicity reflects a relaxed promoter specificity rather than a regulatory role of promoter selection. Nearly half the identified transcription initiation sites displayed immediately upstream a CRTA core sequence, which was mostly seen within the previously described CRTAAGAGA promoter motif or a novel CGTATATAA promoter element. About as many promoters possessed an ATTA or RGTA core. Our data indicate that the majority of mitochondrial promoters in Arabidopsis deviate significantly from the nonanucleotide consensus derived earlier for dicot mitochondrial promoters.

Arabidopsis↗
PubMed1998

Inhibition of mitochondrial gene expression by antisense RNA of mitochondrial transcription factor A (mtTFA).

Mitochondrial transcription factor A (mtTFA) plays an important role in regulating the expression of mitochondrial genes. To gain a better understanding of the relationships between mitochondrial gene expression and mtTFA, the mtTFA gene was inserted into a mammalian expression vector, both in the sense orientation and in the antisense orientation. After construction, these plasmids were transfected into COS-7 cells. In antisense-transformed cells, the expression of the cytochrome c oxidase subunit I and subunit III genes encoded by mitochondrial DNA was inhibited and there was an accompanying reduction of the level of mtTFA protein. These results provide direct evidence that the expression of mitochondrial genes is under the control of mtTFA.

Animals↗
PubMed2005

Time-course of mitochondrial gene expressions in mice brains: implications for mitochondrial dysfunction, oxidative damage, and cytochrome c in aging.

The study of aging is critical for a better understanding of many age-related diseases. The free radical theory of aging, one of the prominent aging hypotheses, holds that during aging, increasing reactive oxygen species in mitochondria causes mutations in the mitochondrial DNA and damages mitochondrial components, resulting in senescence. Understanding a mitochondrial gene expression profile and its relationship to mitochondrial function becomes an important step in understanding aging. The objective of the present study was to determine mRNA expression of mitochondrial-encoded genes in brain slices from C57BL6 mice at four ages (2, 12, 18, and 24 months) and to determine how these altered mitochondrial genes influence age-related changes, including oxidative damage and cytochrome c in apoptosis. Using northern blot analysis, in situ hybridization, and immunofluorescence analyses, we analyzed changes in the expression of mitochondrial RNA encoding the mitochondrial genes, oxidative damage marker, 8-hydroxyguanosine (8-OHG), and cytochrome c in brain slices from the cortex of C57BL6 mice at each of the four ages. Our northern blot analysis revealed an increased expression of mitochondrial-encoded genes in complexes I, III, IV, and V of the respiratory chain in 12- and 18-month-old C57BL6 mice compared to 2-month-old mice, suggesting a compensatory mechanism that allows the production of proteins involved in the electron transport chain. In contrast to the up-regulation of mitochondrial genes in 12- and 18-month-old C57BL6 mice, mRNA expression in 24-month-old C57BL6 mice was decreased, suggesting that compensation maintained by the up-regulated genes cannot be sustained and that the down-regulation of expression results in the later stage of aging. Our in situ hybridization analyses of mitochondrial genes from the hippocampus and the cortex revealed that mitochondrial genes were over-expressed, suggesting that these brain areas are critical for mitochondrial functions. Our immunofluorescence analysis of 8-OHG and cytochrome c revealed increased 8-OHG and cytochrome c in 12-month-old C57BL6 mice, suggesting that age-related mitochondrial oxidative damage and apoptosis are associated with mitochondrial dysfunction. Our double-labeling analysis of in situ hybridization of ATPase 6 and our immunofluorescence analysis of 8-OHG suggest that specific neuronal populations undergo oxidative damage. Further, double-labeling analysis of in situ hybridization of ATPase 6 and immunofluorescence analysis of cytochrome c suggest cytochrome c release is related to mitochondrial dysfunction in the aging C57BL6 mouse brain. This study also suggests that these mitochondrial gene expression changes may relate to the role of mitochondrial dysfunction, oxidative damage, and cytochrome c in aging and in age-related diseases such as Alzheimer's disease and Parkinson's disease.

Aging↗