Atg8a interacts with transcription factor Sequoia to control the expression of autophagy genes in Drosophila

Jacomin, A.-C.; Petridi, S.; DiMonaco, M.; Jain, A.; Bhujabal, Z.; Mulakkal, N.; Palara, A.; Powell, E.; Chung, B.; Zampronio, C.; Jones, A.; Cameron, A.; Johansen, T.; Nezis, I.

doi:10.1101/611731

bioRxiv · 10.1101/611731

Atg8a interacts with transcription factor Sequoia to control the expression of autophagy genes in Drosophila

Jacomin, A.-C.·Petridi, S.·DiMonaco, M.·Jain, A.·Bhujabal, Z.·Mulakkal, N.·Palara, A.·Powell, E.·Chung, B.·Zampronio, C.·Jones, A.·Cameron, A.·Johansen, T.·Nezis, I.

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Abstract

Autophagy is a fundamental, evolutionarily conserved, process in which cytoplasmic material is degraded through the lysosomal pathway [1-7]. One of the most important and well-studied autophagy-related proteins is LC3 [Microtubule-associated protein 1 light chain 3, (called Atg8 in yeast and Drosophila)], which participates in autophagosome formation and autophagy cargo selection in the cytoplasm, and is one of the most widely utilized markers of autophagy [8, 9]. Despite growing evidence that LC3 is enriched in the nucleus, little is known about the mechanisms involved in targeting LC3 to the nucleus and the nuclear components it interacts with [10-13]. Here we show that Drosophila Atg8a protein, homologous to mammalian LC3 and yeast Atg8, 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 also show that Atg8a interacts with YL-1, a component of a nuclear acetyltransferase complex, and is acetylated at position K46. Additionally, we 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.

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Jacomin, A.-C., Petridi, S., DiMonaco, M., Jain, A., Bhujabal, Z., Mulakkal, N., Palara, A., Powell, E., Chung, B., Zampronio, C., Jones, A., Cameron, A., Johansen, T., Nezis, I.. 2019-04-17. Atg8a interacts with transcription factor Sequoia to control the expression of autophagy genes in Drosophila. https://doi.org/10.1101/611731

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