Novel Insights into the Regulation of Autophagy in Saccharomyces Cerevisiae

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Title: Novel Insights into the Regulation of Autophagy in Saccharomyces Cerevisiae
Author: Wu, Xi
Abstract: Autophagy is an evolutionarily conserved pathway for the degradation of intracellular contents . How autophagy is regulated , especially upon changes in metabolic and nutritional state , remains poorly understood . In Saccharomyces cerevisiae , autophagy is normally triggered by nutrient starvation . However , by using a prototrophic strain , I discovered that autophagy can be strongly induced upon switch from a rich medium (YPL ) to a minimal medium (SL ) without nutrient starvation . This new autophagy -inducing condition was termed SL -induced autophagy . Growth measurement confirmed that SL -induced autophagy was important for cellular homeostasis and growth following medium switch . A genetic screen uncovered IML1 , NPR2 , NPR3 and PBP1 , which are all required for SL -induced autophagy , but not for nitrogen -starvation -induced autophagy . Iml1p , Npr2p and Npr3p function in the same complex and regulate autophagosome formation . During SL -induced autophagy , Iml1p can localize to the pre -autophagosomal structures , consistent with the role of the Iml1p complex in autophagosome formation . Moreover , a conserved domain in Iml1p was identified to be required for SL -induced autophagy as well as complex formation . I discovered that sulfur containing amino acids , but not non -sulfur containing amino acids , can specifically inhibit SL -induced autophagy . I further demonstrated that cysteine is a key metabolite that inhibits SL -induced autophagy by regulating cellular processes related to cysteine metabolism . Cysteine does not suppress SL -induced autophagy by regulating oxidative stress , protein urmylation and thiolation of cytosolic tRNAs . Future studies will be required to reveal the exact mechanism through which cysteine inhibits SL -induced autophagy . I also discovered that autophagy can be significantly induced upon depletion of a Fe -S cluster containing protein , Rli1p , and other factors that are also involved in rRNA processing and translation initiation . Interestingly , IML1 , NPR2 , NPR3 and PBP1 are also important for Rli1p -depletion -induced mitophagy . These results strongly suggest the mechanistic link between SL -induced autophagy and ribosome biogenesis or translation regulation . Collectively , my studies have demonstrated the existence of additional mechanisms that regulate autophagy in response to relatively more subtle changes in metabolic and nutritional state .
URI: http : / /hdl .handle .net /2152 .5 /957
Date: 2011-12-15


Novel Insights into the Regulation of Autophagy in Saccharomyces Cerevisiae. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /957 .

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