Hypoxia is a major stressor at high altitudes that limits tissue oxygen availability. High altitude environments are also extremely cold which increases thermogenic demand. Small mammals living at high altitude face the competing energetic challenge of maintaining thermogenesis in a hypoxic environment that can impair aerobic ATP supply. It has been suggested that hypoxia-induced impairments in ATP synthesis capacity and cold-induced increases in thermogenic demand could be counteracted by an increase in tissue oxidative capacity and/or fuel selection. As the organelle that consumes oxygen to produce ATP, changes in mitochondrial physiology can help offset physiological impairments at high altitudes. We explored this hypothesis in North American deer mice (Peromyscus maniculatus), from populations native to high and low altitude. We compared mitochondrial volume densities, intracellular distribution, respiratory capacities, enzyme activities of the mitochondrial complexes, capillarity, and fibre-type distribution in skeletal and cardiac muscles. To examine potential changes to mitochondrial physiology at high altitudes deer mice (P. maniculatus) were acclimated to: warm (25°C) normoxia; warm hypoxia (simulated altitude of 4300m); cold (5°C) normoxia; and cold + hypoxia. In skeletal muscle, highlanders had higher mitochondrial volume densities than lowlanders, entirely due to an increased abundance of mitochondria in a subsarcolemmal location next to capillaries. Mitochondria from highland mice also had higher mitochondrial respiratory capacities and cytochrome c oxidase activity in control conditions, but these values converged after hypoxia acclimation. Cold acclimation restored pyruvate and fatty acid respiratory capacity to control levels in highland mice, which also showed an increase in mitochondrial uncoupling. Cold increased respiratory capacities in lowland mice. Acclimation to cold+hypoxia did not change mitochondrial physiology beyond cold alone and appeared to counteract the effects of hypoxia on highland mice. In cardiac muscle highland mice had higher respiratory capacities, but after hypoxia acclimation lowland mice significantly increased respiratory capacities. In response to hypoxia, highland mice increased the relative capacity to oxidize carbohydrates compared to fatty acids. Our results suggest that both highland ancestry and plasticity affect mitochondrial physiology, and likely contributes to performance at high altitudes. / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/21480 |
| Date | January 2017 |
| Creators | Mahalingam, Sajeni |
| Contributors | McClelland, Grant, Scott, Graham, Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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