| Research Abstract |
Autophagy is a main route for sequestration of cytoplasmic components to lysosome/vacuole. Genetic analyses revealed at least 15 genes (APG and AUT) are required for the autophagy in yeast. These genes play roles on autophagosome(AP) formation, unique membrane dynamics in autophagy. Among them about half are involved in ubiquitination like conjugation systems. Apg12 is activated by Apg7 (E1), transferred to Apg10 (E2), and finally forms an isopeptide bond with Apg5. Apg12-Apg5 forms a tetrameric complex of Apg12-Apg5/Apg16. Another UBL, Apg8/Aut7 is activated by the same E1 enzyme, Apg7, transferred to Apg3/Aut1, and finally forms a conjugate with membrane phospholipid, PE via an amido bond. Modification of Apg5 by Apgl2 is constitutive and irreversible, while deconjugation of Apg8-PE by Apg4 /Aut2, a processing enzyme of nascent Apg8, is necessary for normal progression of autophagy. These two conjugation systems are similar to ubiquitination mechanistically, but quite distinct from other Ubl systems in several aspects. These two systems may function closely during AP formation, because Apg12-Apg5 and Apg8 colocalize in a perivacuolar structure named PAS and Apg8-PE level is severely reduced by the defect in Apg12 system. PAS, preautophagosomal structure in which many Apg proteins are associated, plays essential roles for AP formation, but its precise structure should be uncovered in future.
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