Date of Award

7-12-2012

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Fusheng Tang

Abstract

Families of oxysterol-binding proteins (OSBP) are proposed to be involved in sterol metabolism. The unique sterol composition of eukaryotic membranes requires proteins such as OSBPs that contribute to sterol homeostasis. This thesis explores the role of Osh proteins (OSBP homologues) in membranes of yeast vacuoles in light of lifespan extension. The results show that over-expression of OSH6 promoted vacuole fusion, an ergosterol-requiring process, and extended the replicative lifespan. It is found that the level of Osh6 decreased with age. This decrease is slowed in a mutant expressing elevated OSH6 levels. It is also found that the sterol-binding domain of Osh6 is essential for the longevity effect. Finally, elevated Osh6 levels resulted in depletion of sterols in the plasma membrane but increased sterols in the vacuolar membrane. These results are consistent with a model that Osh6 extends replicative life span by transporting sterols to the vacuolar membrane and promoting vacuole fusion.

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