Mitochondrial DNA encodes thirteen protein subunits in the oxidative phosphorylation system (OXPHOS) that is responsible for cellular energy production. Mitochondrial disorders have been identified to be associated with mtDNA mutations. However, the molecular mechanisms of specific mtDNA mutations are still being explored in order to establish causative links. This study tries to elucidate the mutational effects of mtDNA on OXPHOS complex activities and cell growths. Using mouse 3T3 fibroblasts as a cell model, single-cell clones with different growth rates were isolated. The entire mtDNA genome was sequenced for mutations. The enzymatic activities of OXPHOS complex I to V were analysed. Three growth patterns represented by five clones were identified. Three clones (clone #2, #3, and #6) had the shortest doubling times (11.5 - 14.9 hours). Clone #1 had a medium growth rate (19.2 hous); and clone #5 had a significantly slow growth rate (22 hours). MtDNA sequencing results revealed that clone #5 had several heteroplasmic mutations (one in 16S rRNA, two in tRNAser (UCN), three in tRNAasp, one in tRNAlys, one in COI, five in COII, and one in ATPase8) while the other four clones showed sequence homology. Enzymatic analyses showed that on average clone #5 had significantly low complex III, IV, and V activities (p < 0.05). Changes in biochemical properties and protein structure were analyzed to deduct possible mechanisms for reduced respiration. In conclusion, the slow growth rate is associated with reduced OXPHOS enzyme functions. It is most likely that the combination of COI and COII mutations resulted in the reduction of complex IV function. It is still unclear whether the ATPase8 mutation (T7869A) in the non-conserved region alone can have such a pronounced phenotypic effect. A reduction in complex III also cannot be explained since there were no mutations in the only mtDNA-encoded complex III gene, but it is possible that there are mutations in the nDNA-encoded complex III genes. Mutations in tRNA and rRNA genes may also be responsible for reduced protein syntheses and consequently reduced OXPHOS activities. It is unclear why complex I activity was not affected. Although the mutational effect of individual mtDNA mutation observed cannot be clearly identified, this study establishes a correlation between mtDNA mutation and cell energy production and growth.

Thesis (M.S. - Soil, Water and Environmental Science)--University of Arizona. / Includes bibliographical references (leaves [64]-69).

Thesis (Ph. D.)--University of Western Sydney, 2002. / "This thesis is submitted in fulfilment of the requirements of the degree of Doctor of Philosophy to the University of Western Sydney School of Biological Sciences."t.p. Includes bibliographical references (leaves 138-150).

Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2008. / Committee Chair: Meredith, Carson; Committee Co-Chair: Galis, Zorina; Committee Co-Chair: McIntire, Larry; Committee Member: García, Andrés; Committee Member: Prausnitz, Mark.

Thesis (M.S.)--Ohio State University, 2008. / Title from first page of PDF file. Includes bibliographical references (p. 75-100).

Thesis (Ph. D.)--University of Sydney, 2008. / Title from title screen (viewed Apr. 27, 2009) Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Discipline of Oral Pathology and Oral Medicine, Faculty of Dentistry. Degree awarded 2008; thesis submitted 2007. Includes bibliography. Also available in print form.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 97-112) Also available in print.

Thesis (Ph. D.)--Ohio State University, 2008. / Title from first page of PDF file. Includes bibliographical references (p. 210-232).

Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 97-112) Also available online.

Thesis (Ph. D.)--University of Canterbury, 2009. / Typescript (photocopy). "January, 2009." Includes bibliographical references (p. 213-227). Also available via the World Wide Web.