Evaluation of metallothionein involvement in the modulation of mitochondrial respiration in mice / Marianne Pretorius.

Metallothioneins (MTs) are small, non-enzymatic proteins that are involved in cellular detoxification and metal homeostasis because of their high cysteine content. MTs have also been identified as one of the vast number of adaptive responses to mitochondrial respiratory chain (RC) deficiencies. Asid...

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Main Author: Pretorius, Marianne
Language:en
Published: North-West University 2013
Subjects:
Online Access:http://hdl.handle.net/10394/9195
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spelling ndltd-NWUBOLOKA1-oai-dspace.nwu.ac.za-10394-91952014-09-30T04:06:15ZEvaluation of metallothionein involvement in the modulation of mitochondrial respiration in mice / Marianne Pretorius.Pretorius, Mariannemitochondrionmetallothioneinoxidative phosphorylationrespiratory chainmitochondrial diseaseMTKO mouse modelcomplex I deficiencyrotenoneenzyme activity analysesmitochondrial respiration analysesMetallothioneins (MTs) are small, non-enzymatic proteins that are involved in cellular detoxification and metal homeostasis because of their high cysteine content. MTs have also been identified as one of the vast number of adaptive responses to mitochondrial respiratory chain (RC) deficiencies. Aside from this, numerous other studies have linked MTs to several mitochondrion-linked components, including reactive oxygen species (ROS) and oxidative stress, apoptosis, glutathione, energy metabolism and nuclear- and mitochondrial DNA transcription regulation. However, most of the reports concerning the putative link between MTs and mitochondria are from in vitro studies and relatively little supportive in vivo evidence has been reported. Information on the involvement of MTs with respiratory chain function is especially limited. Is was therefore the aim of this study to investigate the involvement of MTs in mitochondrial respiration and respiratory chain enzyme function by using an MT knockout (MTKO) mouse model, which was treated with the irreversible complex I inhibiting reagent, rotenone. The aim was achieved by implementing three objectives: firstly, the RC function was investigated as a complete working unit; secondly, the functional and structural properties of single units (enzymes) of the RC were investigated utilising enzyme activity assays and BN- PAGE/western blot analysis; and thirdly, the possible effect of MTs on mtDNA copy number was investigated. While some tendencies of variation in RC enzyme activity and expression were identified, no significant effect on the overall mitochondrial respiratory function, or any significant differences in the relative mtDNA copy number of MTKO mice were observed. Thus it is concluded, while MTs have in this study revealed relatively small changes in respiratory chain function, which may still prove to have biological ignificance in vivo, the exact nature of the putative role of MTs in mitochondrial respiration or oxidative phosphorylation remains undefined.Thesis (MSc (Biochemistry))--North-West University, Potchefstroom Campus, 2012.North-West University2013-10-02T10:49:26Z2013-10-02T10:49:26Z2011Thesishttp://hdl.handle.net/10394/9195en
collection NDLTD
language en
sources NDLTD
topic mitochondrion
metallothionein
oxidative phosphorylation
respiratory chain
mitochondrial disease
MTKO mouse model
complex I deficiency
rotenone
enzyme activity analyses
mitochondrial respiration analyses
spellingShingle mitochondrion
metallothionein
oxidative phosphorylation
respiratory chain
mitochondrial disease
MTKO mouse model
complex I deficiency
rotenone
enzyme activity analyses
mitochondrial respiration analyses
Pretorius, Marianne
Evaluation of metallothionein involvement in the modulation of mitochondrial respiration in mice / Marianne Pretorius.
description Metallothioneins (MTs) are small, non-enzymatic proteins that are involved in cellular detoxification and metal homeostasis because of their high cysteine content. MTs have also been identified as one of the vast number of adaptive responses to mitochondrial respiratory chain (RC) deficiencies. Aside from this, numerous other studies have linked MTs to several mitochondrion-linked components, including reactive oxygen species (ROS) and oxidative stress, apoptosis, glutathione, energy metabolism and nuclear- and mitochondrial DNA transcription regulation. However, most of the reports concerning the putative link between MTs and mitochondria are from in vitro studies and relatively little supportive in vivo evidence has been reported. Information on the involvement of MTs with respiratory chain function is especially limited. Is was therefore the aim of this study to investigate the involvement of MTs in mitochondrial respiration and respiratory chain enzyme function by using an MT knockout (MTKO) mouse model, which was treated with the irreversible complex I inhibiting reagent, rotenone. The aim was achieved by implementing three objectives: firstly, the RC function was investigated as a complete working unit; secondly, the functional and structural properties of single units (enzymes) of the RC were investigated utilising enzyme activity assays and BN- PAGE/western blot analysis; and thirdly, the possible effect of MTs on mtDNA copy number was investigated. While some tendencies of variation in RC enzyme activity and expression were identified, no significant effect on the overall mitochondrial respiratory function, or any significant differences in the relative mtDNA copy number of MTKO mice were observed. Thus it is concluded, while MTs have in this study revealed relatively small changes in respiratory chain function, which may still prove to have biological ignificance in vivo, the exact nature of the putative role of MTs in mitochondrial respiration or oxidative phosphorylation remains undefined. === Thesis (MSc (Biochemistry))--North-West University, Potchefstroom Campus, 2012.
author Pretorius, Marianne
author_facet Pretorius, Marianne
author_sort Pretorius, Marianne
title Evaluation of metallothionein involvement in the modulation of mitochondrial respiration in mice / Marianne Pretorius.
title_short Evaluation of metallothionein involvement in the modulation of mitochondrial respiration in mice / Marianne Pretorius.
title_full Evaluation of metallothionein involvement in the modulation of mitochondrial respiration in mice / Marianne Pretorius.
title_fullStr Evaluation of metallothionein involvement in the modulation of mitochondrial respiration in mice / Marianne Pretorius.
title_full_unstemmed Evaluation of metallothionein involvement in the modulation of mitochondrial respiration in mice / Marianne Pretorius.
title_sort evaluation of metallothionein involvement in the modulation of mitochondrial respiration in mice / marianne pretorius.
publisher North-West University
publishDate 2013
url http://hdl.handle.net/10394/9195
work_keys_str_mv AT pretoriusmarianne evaluationofmetallothioneininvolvementinthemodulationofmitochondrialrespirationinmicemariannepretorius
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