Date of Award
12-30-2013
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biology
First Advisor
Fusheng Tang
Abstract
Oxysterol-binding protein homolouges (OSH) have been implicated in mediating non-vesicular sterol transport. Caloric restriction (CR) down-regulates sterol synthesis in a variety of organisms, including the budding yeast Saccharomyces cerevisiae. OSH6, when up-regulated, extends replicative lifespan. In contrast, OSH5 up-regulation shortens replicative lifespan. In this thesis I obtained evidence to show that the deletion of OSH5 extends replicative lifespan in normal media. Deletion of OSH5 in the presence of caloric restriction blocks the lifespan-extending properties of the CR media. My data demonstrate that the total cellular sterol levels of the longevity mutants are indistinguishable from that of wild type. This suggests that Osh proteins are involved in the intracellular distribution of sterols. Also it is shown that genetic alterations leading to down-regulation of sterol synthesis actually causes an up-regulation of OSH5 protein levels. Interestingly, OSH5 is required for the longevity effect of the genetically altered "CR mimics": PERG6-OSH6 and PERG6-ERG2. Deletion of OSH5 from the cell slows certain steps in endocytosis, which is also a target of CR. Thus, the role of Osh5 in sterol metabolism is likely that of maintaining sterol levels in specific critical membranes when total sterol levels within the cell are in low supply.
Recommended Citation
Craft, William Douglas, "The OSH Family of Proteins and Their Role in Caloric Restriction-Mediated Lifespan Extension in the Budding Yeast Saccharomyces cerevisiae" (2013). Theses and Dissertations. 476.
https://research.ualr.edu/etd/476
