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

Lookup NU author(s): Dr Satomi Miwa, Dr Conor LawlessORCiD, Professor Thomas von Zglinicki

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Abstract

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 (NaHCO3)-C-14 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.


Publication metadata

Author(s): Miwa S, Lawless C, von Zglinicki T

Publication type: Article

Publication status: Published

Journal: Biochemical Society Transactions

Year: 2010

Volume: 38

Pages: 1322-1328

Print publication date: 01/10/2010

ISSN (print): 0300-5127

ISSN (electronic): 1470-8752

Publisher: Portland Press Ltd.

URL: http://dx.doi.org/10.1042/BST0381322

DOI: 10.1042/BST0381322


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Funding

Funder referenceFunder name
Biotechnology and Biological Sciences Research Council (BBSRC)
BB/C008200/1Engineering and Physical Sciences Research Council (CPSRC)

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