The interaction of diet and mitochondrial DNA on mitochondrial function and organismal fitness

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Embargoed until 2019-03-31
Copyright: Aw, Wen Chyuan
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Abstract
The influence of diet on mitochondrial functions has been a longstanding question in evolutionary biology as well as human health and well-being. Discovering the interaction between diet and mitochondrial DNA (mtDNA) can facilitate a better understanding of organelle and organism evolution and may be a tractable mechanism for improving human health in the age of obesity. Mitochondrial functions are determined by a tight coordination between mtDNA, nuclear DNA and the metabolic state of cells, which is highly influenced by diet. In theory, diet may also affect the selective advantage of different mitochondrial haplotypes. The overall goal of this thesis is to determine the role of diet in changing the mitochondrial functions of the organism. Mitochondria are an important regulator of organismal fitness and a key energy converting organelle. The flow of energy in the biological system involves the conversion of macronutrients to form substrates that drive mitochondrial respiration. The energy generated from mitochondrial respiration will then be invested into different physiological traits for optimising the organism fitness. To study how diet affects mitochondrial functions, I utilise Drosophila fly lines harbouring different mtDNA haplotypes in a constant nuclear background. These lines contain known mtDNA sequence variations and allow me to perform mitochondrial function tests to determine the consequences of specific mutations on mitochondrial and organism health. This thesis is composed of four main studies. The first two studies focus on the development of quantitation protocols that allow me to measure and determine the influence of diet on Drosophila age grading and mitochondrial functions. The last two studies specifically aim to characterise the relationship between diet and mitochondrial functions. Three major conclusions can be drawn from these studies. First, naturally occurring mtDNA variations in Drosophila melanogaster lead to differences in phenotype. Secondly, this variation in phenotypic expression is regulated by mitochondrial functions. Lastly, diet can influence mitochondrial functions and influence the phenotype of the organism. My data show that there is an intricate cross-talk between diet and mtDNA where mtDNA haplotypes show specific responses toward dietary change. Particularly, I have demonstrated that nonsynonymous mtDNA mutations may be slightly deleterious in one diet but confer beneficial effects when exposed to an alternate diet.
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Author(s)
Aw, Wen Chyuan
Supervisor(s)
Ballard, J.W.O
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Publication Year
2017
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
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