Role for the ESCRT complex in the relationship between nutrient signaling and autophagy in Saccharyomyces cerevisae

ESCRT;Nutrient sensing;Autophagy;not listed

Sing, Cierra Nicole

Johns Hopkins University

关键词: ESCRT;    Nutrient sensing;    Autophagy;    not listed;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/37259/SING-THESIS-2014.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Nutrient sensing is a vital cellular pathway used by all organisms to synchronize their cellular proliferation to correspond with their nutritional status through TOR (target of rapamycin) regulation. Therefore, when cells sense a low nutrient environment, cellular proliferation is halted and autophagy is initiated. Autophagy is a protective mechanism to allow cells to recycle, self-eat, their expended organelles for energy and survival. The relationship between nutrient sensing and autophagy is imperative for proper cellular growth, and when defective, can result in detrimental onset of various diseases. Results of a high-throughput screening of the yeast knockout collection of Saccharyomyces cerevisiae by Teng and the Hardwick lab identified knockout strains that lack components of the ESCRT pathway, which is conserved from yeast to mammals, resulted in a growth phenotype in low amino acid medium. These knockout strains failed to halt proliferation in low amino acid conditions, thus proceeded to outgrow wild type. Yeast screen also revealed a group of strains expressed phenotypes derived from a secondary mutation, rather than the original knockout gene.Although, tetrad dissections I executed on the ESCRT knockout strains confirmed the opposite, phenotypes were derived from the original knockout gene and were not due to a secondary mutations. This knowledge allows for a direct extrapolation of experimental results to be directly related to the gene deletions itself. ESCRTs dynamic ability to curve membranes and create multivesicular bodies provides exceptional functionality and mobility for various cellular mechanisms. I hypothesize that there are more ESCRT functions to be uncovered. I propose that the multivesicular body biogenesis provides an excellent vehicle to relay nutrient signals to properly correlate cell growth with its external and internal environments. When correlation is dysregulated improper cell growth occurs under nutrient improvished conditions. My research further investigated the phenotypes of ESCRT strains in relation to TOR and autophagy under nutrient deprivation reveals new insights into ESCRT functions. Evidence show ESCRT protein expression of subcomplexes I and III expressed a defect in TOR kinase regulatory activity due to the maintenance of Tor activity, and or increasing Tor activity during times of nutrient withdrawal. My data suggest new functions of yeast ESCRTs by possibly conveying nutrient signaling through multivesicular bodies.My studies on nutrient signaling emphasizes the critical role of this vital pathway for cellular organisms, and when defective can be detrimental to a cell’s ability to effectively sustain life. Defects in TOR can lead to accelerated aging, cancer, and epilepsy. The links between ESCRTs, nutrient signaling, and human health are only just the beginning to be uncovered.