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PROTEOSTASIS IN BUDDING YEAST
Zhou, Chuankai
Zhou, Chuankai
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Abstract
Cells utilize an array of quality control mechanisms to maintain a stable and functional proteome. These protein homeostasis mechanisms counteract the constant challenges of protein damages through an integrated network of chaperones, the ubiquitin-proteasome system and autophagy. Loss of protein homeostasis leads to formation of protein aggregates, a phenomenon underlies aging and the progression of numerous neurodegenerative diseases characterized by the deposition of protein aggregates and mitochondrial dysfunction. During cell division, aggregates formed by damaged proteins are segregated asymmetrically such that the damaged proteins are not inherited by the sibling cell with important biological potentials, such as longevity and stemness. In my studies, I examined the dynamics of protein aggregates, including formation, motility, asymmetric segregation and dissolution, in budding yeast to understand the mechanisms used to maintain a functional proteome in this eukaryotic cell. The results of my thesis have revealed that: 1) the aggregation of cytosolic misfolded proteins requires new polypeptide synthesis and is restricted to the surface of mitochondria and ER, which harbors the majority of active translation sites; 2) the motility of aggregates can be characterized as random walk with confinement cast by the associated organelles; 3) the geometry of bud neck, together with the confinement, largely precludes the leakage of protein aggregates during the polarized growth of daughter cells; 4) Sir2p is not directly involved in the aggregate dynamics; 5) mitochondria contribute to the dissolution of cytosolic aggregates by importing and degrading the proteins trapped in the aggregates. Thus, the sophisticated interactions between different cellular structures influence the dynamics of protein aggregates and the cytosolic proteostasis.
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Date
2016-08-31
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University of Kansas
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Keywords
Biology, Cellular biology, Aging, aging, asymmetric segregation, budding yeast, mitochondria, protein aggregation, proteostasis