Self-Regulation of Autophagy Genes Expression by Atg8a and Its Interacting Partners YL-1, Sequoia and Sir2 In Drosophila
33 Pages Posted: 4 Dec 2019 Publication Status: Review CompleteMore...
Autophagy is a process in which cytoplasmic material is degraded through the lysosomal pathway. One of the most studied autophagy-related proteins is LC3, which participates in autophagosome formation and autophagy cargo selection in the cytoplasm. Despite growing evidence that LC3 is enriched in the nucleus, little is known about the nuclear components it interacts with. Here we show that Drosophila Atg8a protein, homologous to mammalian LC3, interacts with the transcription factor Sequoia in a LIR-motif dependent manner. We show that Sequoia depletion induces autophagy in nutrient rich conditions through enhanced expression of autophagy genes. We show that Atg8a interacts with YL-1, a component of a nuclear acetyltransferase complex and that it is acetylated in nutrient rich conditions. We also show that Atg8a interacts with the deacetylase Sir2, which deacetylates Atg8a during starvation in order to activate autophagy. Our results suggest a mechanism of regulation of expression of autophagy genes by Atg8a, which is linked to its acetylation status and its interaction with Sequoia, YL-1 and Sir2.
Keywords: acetylation, autophagy, LIR motif, nucleus, transcription, LC3/Atg8
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