scholarly journals CONTROL OF MITOCHONDRIAL TURNOVER UNDER THE INFLUENCE OF THYROID HORMONE

1971 ◽  
Vol 48 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Nicholas J. Gross
Keyword(s):  
Mitochondrial Dna ◽  
Thyroid Hormone ◽  
Rat Heart ◽  
Major Part ◽  
Mitochondrial Protein ◽  
Turnover Rates ◽  
Physiological Conditions ◽  
Hormone Administration ◽  
Mitochondrial Turnover ◽  
Liver Changes

The effect of thyroid hormone on the turnover of mitochondrial DNA and protein was studied in rat heart and liver. Changes in turnover were observed in both thyroidectomized and normal rats following administration of thyroid hormone. In heart and liver the turnover of mitochondrial DNA and protein was slower in thyroidectomized rats than in normal rats. The turnover of mitochondrial DNA and protein was affected similarly following the administration of thyroid hormone, suggesting that mechanisms which control turnover of mitochondrial constituents may be predicated upon a major part of the mitochondrion. In heart a decreased rate of degradation contributes to the increase in total mitochondrial protein. Mitochondrial DNA, labeled before administration of thyroid hormone, turns over, after the start of thyroid hormone administration, at a different rate from that in newly synthesized DNA. The different turnover rates suggest that in liver the pre-existing population of mitochondria is being replaced by another population synthesized under new physiological conditions.

Correction of radiolabel pulse–chase data by a mathematical model: application to mitochondrial turnover studies

2010 ◽  
Vol 38 (5) ◽  
pp. 1322-1328 ◽  
Author(s):  
Satomi Miwa ◽  
Conor Lawless ◽  
Thomas von Zglinicki
Keyword(s):  
Mitochondrial Protein ◽  
Distributed Parameter ◽  
General Context ◽  
Parameter Estimates ◽  
Turnover Rates ◽  
Degradation Study ◽  
Important Means ◽  
Inherent Problem ◽  
Full Power ◽  
Mitochondrial Turnover

Metabolic labelling pulse–chase experiments are important means to study molecular turnover rates. However, the inherent problem associated with the method is precursor re-utilization, which can cause a significant overestimation of the actual rates of molecular degradation. In published studies on mitochondrial degradation, this problem has led to widely differing results. Practically, the extra information required to correct these errors is not easy to obtain. Using an example of a mitochondrial protein degradation study with NaH14CO3 as the precursor label, we explain the limitations of the method and our approaches to mathematical correction. A dynamic model, including error, used the full power of the data and resulted in sensitive and specific distributed parameter estimates, helping to reduce numbers of experimental animals. This example has important implications not only for similar pulse–chase experiments, but also in a more general context where comparable types of data are generated.

scholarly journals Regulation of mitochondrial protein turnover by thyroid hormone(s)

1975 ◽  
Vol 152 (2) ◽  
pp. 379-387 ◽  
Author(s):  
Medha S. Rajwade ◽  
Surendra S. Katyare ◽  
Prema Fatterpaker ◽  
Arunachala Sreenivasan
Keyword(s):  
Thyroid Hormone ◽  
Protein Turnover ◽  
Mitochondrial Protein ◽  
Brain Mitochondria ◽  
Mitochondrial Proteins ◽  
Proteinase Activity ◽  
Turnover Rates ◽  
Kidney Mitochondria ◽  
Liver And Kidney ◽  
Protein Components

1. The effect of thyroidectomy on turnover rates of liver, kidney and brain mitochondrial proteins was examined. 2. In the euthyroid state, liver and kidney mitochondria show a synchronous turnover with all protein components showing more or less identical half-lives compared with the whole mitochondria. The brain mitochondrial proteins show asynchronous turnover, the soluble proteins having shorter half-lives. 3. Mitochondrial DNA (m-DNA) of liver and kidney has half-lives comparable with that of whole mitochondria from these tissues. 4. Thyroidectomy results in increased half-lives of liver and kidney mitochondria, with no apparent change in the half-life of brain mitochondria. 5. A detailed investigation of the turnover rates of several protein components revealed a significant decrease in the turnover rates of mitochondrial insoluble proteins from the three tissues under study. 6. The turnover rates of m-DNA of liver and kidney show a parallel decrease. 7. Thus it is apparent that thyroid hormone(s) may have a regulatory role in maintaining the synchrony of turnover of liver and kidney mitochondria in the euthyroid state. Turnover of brain mitochondria may perhaps be regulated by some other factor(s) in addition to thyroid hormone(s). 8. It seems likely that during mitochondrial turnover m-DNA and insoluble proteins may constitute a major unit. 9. The mitochondrial protein contents of the three tissues are not affected by thyroidectomy. 10. No correlation was seen between the turnover rate of mitochondria and cathepsin activity in any of the tissues under study in normal or thyroidectomized animals. 11. On the other hand, mitochondrial proteinase activity shows good correlation with the turnover rates of mitochondria in normal animals, and a parallel decrease in activity comparable with the decreased rates of turnover is observed after thyroidectomy. 12. It is concluded that mitochondrial proteinase activity may play a significant role in their protein turnover.

scholarly journals Influence of thyroid hormone on the in vitro translational activity of specific mRNAs in the rat heart.

1983 ◽  
Vol 258 (12) ◽  
pp. 7738-7745 ◽  
Author(s):  
W H Dillmann ◽  
A Barrieux ◽  
W E Neeley ◽  
P Contreras
Keyword(s):  
Thyroid Hormone ◽  
Rat Heart ◽  
Translational Activity ◽  
Specific Mrnas

scholarly journals Altered regulation of energy homeostasis in older rats in response to thyroid hormone administration

2013 ◽  
Vol 28 (3) ◽  
pp. 1499-1510 ◽  
Author(s):  
Stephane Walrand ◽  
Kevin R. Short ◽  
Lydia A. Heemstra ◽  
Colleen M. Novak ◽  
James A. Levine ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Energy Homeostasis ◽  
Hormone Administration ◽  
Altered Regulation

scholarly journals Differential modulation of expression of the two acylphosphatase isoenzymes by thyroid hormone

1995 ◽  
Vol 311 (2) ◽  
pp. 567-573 ◽  
Author(s):  
P Chiarugi ◽  
G Raugei ◽  
R Marzocchini ◽  
T Fiaschi ◽  
C Ciccarelli ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
State Level ◽  
K562 Cells ◽  
Hormone Treatment ◽  
Differential Regulation ◽  
Rapid Decrease ◽  
Differential Modulation ◽  
Hormone Administration ◽  
Specific Mrna

The modulation of expression of the skeletal muscle and erythrocyte acylphosphatase isoenzymes by thyroid hormone has been investigated. Our results indicate a differential regulation of the two enzymic isoforms by tri-iodothyronine (T3) in K562 cells in culture: an increase in the specific mRNA during T3-stimulation is shown only for the skeletal muscle isoenzyme. A fast and transient T3 induction of the accumulation of the specific mRNA can be observed, reaching a maximum 8 h after hormone treatment and then rapidly decreasing almost to the steady-state level after 24 h. A nuclear run-on assay was performed to explore the mechanisms of this regulation. These studies indicate that T3 induction of skeletal muscle acylphosphatase mRNA is due, at least in part, to a fast and transient increase in the rate of gene transcription, within 4 h after hormone administration. A very rapid decrease is then observed within a further 2 h. T3-dependent accumulation of the mRNA for the skeletal muscle acylphosphatase requires ongoing protein synthesis, as confirmed by inhibition with cycloheximide or puromycin. These findings indicate that the transcriptional regulation of the gene may be indirect.

Abstract 89: MitoTimer Mouse: a Novel Tool for the Study of Mitochondrial Turnover in vivo

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Aleksandr B Stotland ◽  
Jennifer Ramil ◽  
Roberta A Gottlieb
Keyword(s):  
Cardiac Tissue ◽  
Fluorescent Protein ◽  
Signal Sequence ◽  
Green Fluorescence ◽  
Physiological Conditions ◽  
High Membrane Potential ◽  
Mitochondrial Turnover ◽  
Single Mitochondrion ◽  
Degree Of Heterogeneity

In order to study mitochondrial turnover at the level of a single mitochondrion, our laboratory has developed the MitoTimer protein. Timer is a mutant of DsRed fluorescent protein developed by Terskikh et al. The Timer protein transitions from green fluorescence to a more stable red conformation as it matures over a span of 48 h. Furthermore, the protein is very stable under physiological conditions, insensitive to variations in ionic strength, and changes in pH between 7.0 and 8.0. Notably, Timer maturation from green to red is significantly slowed in deoxygenated buffer, suggesting that molecular oxygen plays a part in fluorophore maturation. We fused the Timer protein with the mitochondrial signal sequence from the cytochrome c oxidase subunit VIII (COX8) to target the protein to the inner membrane of the mitochondria, and further cloned the protein into a construct with a cardiac-restricted α-myosin heavy chain promoter. This construct was used to create the α-MHC MitoTimer mice. Surprisingly, initial analysis of the hearts from these mice reveals a remarkable degree of heterogeneity in the ratio of red-to- green fluorescence of MitoTimer in cardiac tissue. Furthermore, individual mitochondria within cardiomyocytes display a higher red-to-green fluorescence, implying a block in import of newly synthesized MitoTimer that would be caused by the lack of a high membrane potential, indicative of older, dysfunctional mitochondria. Initial studies suggest that these mice represent an elegant tool for the investigation of mitochondrial turnover in the heart.

Assignment of two mitochondrially synthesized polypeptides to human mitochondrial DNA and their use in the study of intracellular mitochondrial interaction

1982 ◽  
Vol 2 (1) ◽  
pp. 30-41
Author(s):  
N A Oliver ◽  
D C Wallace
Keyword(s):  
Mitochondrial Dna ◽  
Restriction Site ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Synthesis ◽  
Human Mitochondrial Dna ◽  
Ht1080 Cells ◽  
Mitochondrial Dnas ◽  
A Cell ◽  
Dna Restriction ◽  
Restriction Site Polymorphisms

Two mitochondrially synthesized marker polypeptides, MV-1 and MV-2, were found in human HeLa and HT1080 cells. These were assigned to the mitochondrial DNA in HeLa-HT1080 cybrids and hybrids by demonstrating their linkage to cytoplasmic genetic markers. These markers include mitochondrial DNA restriction site polymorphisms and resistance to chloramphenicol, an inhibitor of mitochondrial protein synthesis. In the absence of chloramphenicol, the expression of MV-1 and MV-2 in cybrids and hybrids was found to be directly proportional to the ratio of the parental mitochondrial DNAs. In the presence of chloramphenicol, the marker polypeptide linked to the chloramphenicol-sensitive mitochondrial DNA continued to be expressed. This demonstrated that resistant and sensitive mitochondrial DNAs can cooperate within a cell for gene expression and that the CAP-resistant allele was dominant or codominant to sensitive. Such cooperation suggests that mitochondrial DNAs can be exchanged between mitochondria.

scholarly journals LPS-Induced Endotoxemia Evokes Epigenetic Alterations in Mitochondrial DNA That Impacts Inflammatory Response

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2282
Author(s):  
Björn Koos ◽  
Eva Lotta Moderegger ◽  
Katharina Rump ◽  
Hartmuth Nowak ◽  
Katrin Willemsen ◽  
...  
Keyword(s):  
Immune Response ◽  
Mitochondrial Dna ◽  
Dna Methyltransferase ◽  
Protein Import ◽  
Mononuclear Cells ◽  
Mitochondrial Protein ◽  
Mitochondrial Fraction ◽  
Protein Abundance ◽  
Peripheral Blood Mononuclear ◽  
Cellular Expression

Mitochondrial DNA (mtDNA) plays a vital role as a damage-associated molecular pattern in sepsis being able to shape the immune response. Since pathogen recognition receptors of innate immune cells are activated by demethylated DNA only, we set out to investigate the amount of DNA methyltransferase 1 (DNMT1) in mitochondria and the extent of mtDNA methylation in a human endotoxin model. Peripheral blood mononuclear cells of 20 healthy individuals were isolated from whole blood and stimulated with lipopolysaccharide (LPS) for 48 h. Subsequently, DNMT1 protein abundance was assessed in whole cells and a mitochondrial fraction. At the same time, methylation levels of mtDNA were quantified, and cytokine expression in the supernatant was measured. Despite increased cellular expression of DNMT1 after LPS stimulation, the degree of mtDNA methylation slightly decreased. Strikingly the mitochondrial protein abundance of DNMT1 was reduced by 50% in line with the lower degree of mtDNA methylation. Although only modest alterations were seen in the degree of mtDNA methylation, these strongly correlated with IL-6 and IL-10 expression. Our data may hint at a protein import problem for DNMT1 into the mitochondria under LPS stimulation and suggest a role of demethylated mtDNA in the regulation of the inflammatory immune response.

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