| Summary: | 碩士 === 國立臺灣大學 === 動物學研究所 === 99 === Autophagy is a highly conserved degradation pathway among all eukaryotes that can be induced under stress conditions, such as starvation. During the process, portions of cytoplasm are non-selectively engulfed into double-membrane vesicles called autophagosomes and subsequently delivered to the vacuole for degradation. The small molecules released from the process can be used to maintain cellular homeostasis. However, the degradation processes can occur selectively to remove excess or damaged organelles, for example, pexophagy and mitophagy. In the budding yeast Saccharomyces cerevisiae, the cytoplasm-to-vacuole targeting (Cvt) pathway is a unique type of selective autophagy that is constitutively active in growth condition for biosynthetic transport of vacuolar enzymes, such as precursors of aminopeptidase I and α-mannosidase. Although the Cvt pathway shares the same core machinery with bulk autophagy, it also requires specific regulatory proteins. In this study, I used the Cvt pathway as a model for analyzing the regulatory mechanisms underlying selective autophagy and investigated the role of selective autophagy-specific regulatory protein Atg24.
Atg24 is a PI3P-binding protein essential for selective autophagy but not bulk autophagy. Moreover, Atg24 is also involved in the endosome-to-Golgi protein traffic. I found that Atg24 participates in the vesicle formation step of the Cvt pathway and its recruitment to the PAS (pre-autophagosomal structure) is regulated by the PI3K complex I, Atg20 and Trs85. Besides, Atg24 contains two coiled-coil domains at the C terminus. Only the coiled-coil domain 1 is necessary for selective autophagy, whereas both two coiled-coil domains are required for retrieval of Snc1 in endomembrane trafficking. Although the coiled-coil domain 1 of Atg24 does not mediate its association with known interaction partners Atg17 and Atg20, it determines the subcellular localization of itself as well as Atg20. Our data suggested that during the Cvt pathway, the Atg24-Atg20 complex appears at the PAS in a mutually dependent manner and together they directly assist the Cvt vesicle formation. Future studies are needed to characterize how Atg24 cooperates with the core autophagic machinery in details.
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