Browsing by Subject "Mitochondrial"
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Item Mitochondrial and nuclear assessment of Ferruginous Pygmy-Owl (Glaucidium Brasilianum) Phylogrography(Texas A&M University, 2006-08-16) Proudfoot, Glenn ArthurSequences of the cytochrome b gene and genotypes from 11 polymorphic microsatellite loci were used to assess phylogeographic variation in ferruginous pygmy-owls (Glaucidium brasilianum) from Arizona, Mexico, and Texas. Analysis of mtDNA indicated that pygmy-owl populations in Arizona and Texas are unique, with no shared haplotypes. Populations from Sonora and Sinaloa, Mexico, were distinct from remaining populations in Mexico and grouped closest to haplotypes in Arizona. Nested clade analysis of mtDNA sequence data indicated past fragmentation separated pygmy-owls into two major groups: 1) Arizona, Sonora and Sinaloa, Mexico, and 2) southwestern (Nayarit and Michoacan), south-central (Oaxaca and Chiapas), and eastern Mexico, along the eastern slope of the Sierra Madre Oriental from Texas to Central America. In addition, analysis of mtDNA variation in several species of Glaucidium support the recommendation that populations of G. brasilianum from Mexico, Texas, and Arizona represent a phylogenetically distinct group from populations occurring in South America. The level of separation between the North and South Americanpopulations justifies granting species status (G. ridgwayi) to the North American population. Analysis of distance matrices derived from genotypes of 11 polymorphic microsatellite loci supports restricted gene flow between pygmy-owl populations in Arizona-Sonora and Sinaloa, and Texas-Tamaulipas and the remainder of states in Mexico. The Arizona-Sonora population showed signs of a recent genetic bottleneck, an observation supported by low population estimates for Arizona (13-117 individuals). Heterozygosity in Arizona, however, was equal to levels recorded throughout Mexico and Texas. Congruent patterns revealed by both mtDNA and nuclear DNA (microsatellites) indicate Arizona and Texas populations are distinct subspecies that require the design and implementation of separate management plans for recovery and conservation efforts.Item Mitochondrial uncoupling protein 3 blocks skin carcinogenesis and drives bulge stem cell differentiation and epidermal turnover(2009-05) Lago, Cory Ungles; Mills, Edward MichaelMalignant cells increase glycolysis and down regulate mitochondrial respiration for ATP production. Mechanisms for respiratory impairment in cancerous cells and their importance for carcinogenesis are not well defined. We found that expression of the respiration-inducing uncoupling protein 3 (UCP3) was normally expressed in murine skin and was greatly decreased in cutaneous malignancies. To better understand the significance of UCP3 in epidermal biology and to test the importance of respiratory changes in cancer development, we generated hemizygous mice expressing a keratin-5 promoter-UCP3 transgene (K5-UCP3). Compared to wild type, K5-UCP3 mice exhibited increased cutaneous mitochondrial respiration, had decreased mitochondrial membrane potential in isolated keratinocytes, and were completely resistant to chemically-induced skin carcinogenesis. We showed that the mechanism of UCP3-dependent cancer protection is most likely not due to increased intracellular heat production or ATP depletion in pre-cancerous cells. Therefore, because hair follicle "bulge" stem cells (bSC) are K5⁺ and progenitors of cutaneous carcinomas, we hypothesized that K5-UCP3 animals were protected from skin carcinogenesis due to alterations in their bSC population. Unlike WT, most (85%) hair follicle bulge regions in K5-UCP3 mice lost biochemical markers of quiescent bSC, but bSC functions were fully intact. Supporting our hypothesis that increased skin turnover protected K5-UCP3 mice from skin cancer; we showed that basal keratinocyte cell cycling was increased 3% in K5-UCP3 skin compared to WT. Moreover, the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induced similar proliferative responses in both WT and K5-UCP3 skin, but the magnitude of TPA-induced skin thickening was greatly decreased in K5-UCP3 versus WT mice. Together with microarray, histochemical and in vitro morphologic analyses showing that keratinocyte differentiation was sharply increased in K5-UCP3 skin, this implies that UCP3 may increase keratinocyte transit from stem to differentiated daughter cells. Thus, the cancer resistance mechanism in K5-UCP3 mice likely stems from UCP3-induced mitochondrial respiration, which promotes the differentiation and abrogates the tumorigenicity of progenitor keratinocytes. This is the first demonstration in any context that UCP3 blocks carcinogenesis and promotes cellular differentiation. These observations support Warburg's contention that respiratory dysfunction promotes cancer development, and suggest that mitochondrial uncoupling may be a novel target for cancer prevention and treatment.