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 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.

A Methodology for Optimal Sensor Locations for Identification of Dynamic Systems

1978 ◽  
Vol 45 (1) ◽  
pp. 188-196 ◽  
Author(s):  
P. C. Shah ◽  
F. E. Udwadia
Keyword(s):  
Dynamic Systems ◽  
Distributed Parameter ◽  
Parameter Estimates ◽  
Finite Sample ◽  
Finite Dimensional Representation ◽  
Ground Shaking ◽  
Finite Dimensional ◽  
Suitable Norm ◽  
Shear Beam ◽  
Single Sensor

The problem of optimally positioning sensors in lumped and distributed parameter dynamic systems for the purpose of system identification from time-domain input-output data is formulated and a methodology for its solution is presented. A linear relation between small perturbations in a finite-dimensional representation of the system parameters and a finite sample of observations of the system time response is used to determine approximately the covariance of the parameter estimates. The locations of a given number of sensors are then determined such that a suitable norm of the covariance matrix is minimized. The methodology is applied to the problem of optimally locating a single sensor in a building structure modeled by a shear beam, such that the estimates of the stiffness distributions, obtained from the records of strong ground shaking and the building response at the sensor location, are least uncertain.

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.

Parameter Estimation for Highly Nonlinear Models With Noisy Data

2003 ◽  
Author(s):  
A. F. Emery ◽  
D. Bardot
Keyword(s):  
Nonlinear Models ◽  
Distributed Parameter ◽  
Parameter Estimates ◽  
Confidence Limits ◽  
Nonlinear Functions ◽  
Thermal Systems ◽  
Nonnormal Distributions ◽  
Estimated Parameters ◽  
Highly Nonlinear ◽  
Normally Distributed

Thermal properties are generally determined through solving inverse problems. Because the temperature is a non-linear function of the properties, the solutions are usually effected by linearizing the equations. The statistics of these linearized estimates are based upon the assumptions that the measurement noise has zero mean and is normally distributed, yielding unbiased and normally distributed parameter estimates. In fact, even for this type of noise, nonlinear functions can lead to bias and nonnormal distributions of estimated properties. We examine these effects and show that for typical thermal systems that while the estimates are unbiased and normal, the confidence limits may be inaccurately defined and the residuals of the fits may not be zero mean and uncorrelated. Characterizing the estimated parameters is critical when nonlinear models are to be used for extrapolation.

scholarly journals Pharmacokinetic Models for FcRn-Mediated IgG Disposition

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Jim J. Xiao
Keyword(s):  
Binding Capacity ◽  
Simulated Data ◽  
Parameter Estimates ◽  
Model Parameters ◽  
Pharmacokinetic Models ◽  
Turnover Rates ◽  
Lysosomal Degradation ◽  
Pbpk Models ◽  
Physiologically Based ◽  
Parameter Values

The objectives were to review available PK models for saturable FcRn-mediated IgG disposition, and to explore an alternative semimechanistic model. Most available empirical and mechanistic PK models assumed equal IgG concentrations in plasma and endosome in addition to other model-specific assumptions. These might have led to inappropriate parameter estimates and model interpretations. Some physiologically based PK (PBPK) models included FcRn-mediated IgG recycling. The nature of PBPK models requires borrowing parameter values from literature, and subtle differences in the assumptions may render dramatic changes in parameter estimates related to the IgG recycling kinetics. These models might have been unnecessarily complicated to address FcRn saturation and nonlinear IgG PK especially in the IVIG setting. A simple semimechanistic PK model (cutoff model) was developed that assumed a constant endogenous IgG production rate and a saturable FcRn-binding capacity. The FcRn-binding capacity was defined as MAX, and IgG concentrations exceeding MAX in endosome resulted in lysosomal degradation. The model parameters were estimated using simulated data from previously published models. The cutoff model adequately described the rat and mouse IgG PK data simulated from published models and allowed reasonable estimation of endogenous IgG turnover rates.

scholarly journals Mitochondrial protein turnover: Methods to measure turnover rates on a large scale

2015 ◽  
Vol 78 ◽  
pp. 54-61 ◽  
Author(s):  
X’avia C.Y. Chan ◽  
Caitlin M. Black ◽  
Amanda J. Lin ◽  
Peipei Ping ◽  
Edward Lau
Keyword(s):  
Protein Turnover ◽  
Large Scale ◽  
Mitochondrial Protein ◽  
Turnover Rates

scholarly journals Regulation of mitochondrial proteostasis by the proton gradient

2021 ◽  
Author(s):  
Maria Patron ◽  
Daryna Tarasenko ◽  
Hendrik Nolte ◽  
Mausumi Ghosh ◽  
Yohsuke Ohba ◽  
...  
Keyword(s):  
Protein Turnover ◽  
Mitochondrial Protein ◽  
Proton Gradient ◽  
Turnover Rates ◽  
Mitochondrial Proteome ◽  
Mitochondrial Inner Membrane ◽  
Proteomic Approach ◽  
Adaptive Processes ◽  
Respiratory Complex I ◽  
Gradient Coupling

Mitochondria adapt to different energetic demands reshaping their proteome. Mitochondrial proteases are emerging as key regulators of these adaptive processes. Here, we use a multi-proteomic approach to demonstrate regulation of the m-AAA protease AFG3L2 by the mitochondrial proton gradient, coupling mitochondrial protein turnover to the energetic status of mitochondria. We identify TMBIM5 (previously also known as GHITM or MICS1) as a Ca2+/H+ exchanger in the mitochondrial inner membrane, which binds to and inhibits the m-AAA protease. TMBIM5 ensures cell survival and respiration, allowing Ca2+ efflux from mitochondria and limiting mitochondrial hyperpolarization. Persistent hyperpolarization, however, triggers degradation of TMBIM5 and activation of the m-AAA protease. The m-AAA protease broadly remodels the mitochondrial proteome and mediates the proteolytic breakdown of respiratory complex I to confine ROS production and oxidative damage in hyperpolarized mitochondria. TMBIM5 thus integrates mitochondrial Ca2+ signaling and the energetic status of mitochondria with protein turnover rates to reshape the mitochondrial proteome and adjust the cellular metabolism.

scholarly journals Exercise Enhanced Cardiac Function in Mice With Radiation-Induced Heart Disease via the FNDC5/Irisin-Dependent Mitochondrial Turnover Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Wuyang He ◽  
Yinghong Tang ◽  
Chunqiu Li ◽  
Xiaoyue Zhang ◽  
Shunping Huang ◽  
...  
Keyword(s):  
Heart Disease ◽  
Cardiac Function ◽  
Aerobic Fitness ◽  
Mitochondrial Protein ◽  
Protective Role ◽  
Control Group ◽  
Atp Production ◽  
Elevated Expression ◽  
Radiation Induced ◽  
Mitochondrial Turnover

Background: Despite the development of radiation therapy (RT) techniques, concern regarding the serious and irreversible heart injury induced by RT has grown due to the lack of early intervention measures. Although exercise can act as an effective and economic nonpharmacologic strategy to combat fatigue and improve quality of life for cancer survivors, limited data on its application in radiation-induced heart disease (RIHD) and the underlying molecular mechanism are available.Methods: Fifteen young adult male mice were enrolled in this study and divided into 3 groups (including exercised RIHD group, sedentary RIHD group, and controls; n =5 samples/group). While the mice in the control group were kept in cages without irradiation, those in the exercised RIHD group underwent 3weeks of aerobic exercise on the treadmill after radiotherapy. At the end of the 3rd week following RT, FNDC5/irisin expression, cardiac function, aerobic fitness, cardiomyocyte apoptosis, mitochondrial function, and mitochondrial turnover in the myocardium were assessed to identify the protective role of exercise in RIHD and investigate the potential mechanism.Results: While sedentary RIHD group had impaired cardiac function and aerobic fitness than controls, the exercised RIHD mice had improved cardiac function and aerobic fitness, elevated ATP production and the mitochondrial protein content, decreased mitochondrial length, and increased formation of mitophagosomes compared with sedentary RIHD mice. These changes were accompanied by the elevated expression of FNDC5/irisin, a fission marker (DRP1) and mitophagy markers (PINK1 and LC3B) in exercised RIHD group than that of sedentary RIHD group, but the expression of biogenesis (TFAM) and fusion (MFN2) markers was not significantly changed.Conclusion: Exercise could enhance cardiac function and aerobic fitness in RIHD mice partly through an autocrine mechanism via FNDC5/irisin, in which autophagy was selectively activated, suggesting that FNDC5/irisin may act as an intervening target to prevent the development of RIHD.

Colloidal systems in soils

1994 ◽  
Vol 52 ◽  
pp. 64-65
Author(s):  
J. Thieme ◽  
J. Niemeyer ◽  
P. Guttman
Keyword(s):  
Clay Minerals ◽  
Polymeric Materials ◽  
Spatial Arrangement ◽  
High Specific Surface Area ◽  
Turnover Rates ◽  
Colloidal Systems ◽  
Chemical Conditions ◽  
Aggregation Phenomena ◽  
Iron And Manganese ◽  
Soil Colloids

In soil science the fraction of colloids in soils is understood as particles with diameters smaller than 2μm. Clay minerals, aquoxides of iron and manganese, humic substances, and other polymeric materials are found in this fraction. The spatial arrangement (microstructure) is controlled by the substantial structure of the colloids, by the chemical composition of the soil solution, and by thesoil biota. This microstructure determines among other things the diffusive mass flow within the soils and as a result the availability of substances for chemical and microbiological reactions. The turnover of nutrients, the adsorption of toxicants and the weathering of soil clay minerals are examples of these surface mediated reactions. Due to their high specific surface area, the soil colloids are the most reactive species in this respect. Under the chemical conditions in soils, these minerals are associated in larger aggregates. The accessibility of reactive sites for these reactions on the surface of the colloids is reduced by this aggregation. To determine the turnover rates of chemicals within these aggregates it is highly desirable to visualize directly these aggregation phenomena.

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