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Acetylation of BmAtg8 inhibits starvation-induced autophagy initiation

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Abstract

Silkworm (Bombyx mori) is not only a model organism for scientific studies, but also a commercial insect for agricultural production. BmAtg8 (a B. mori homolog of yeast Atg8) plays crucial roles in macroautophagy (hereafter referred to autophagy), which is helpful for silkworm metamorphosis. Relevant mechanism about BmAtg8 currently remains ambiguous. Based on our previous acetylome of B. mori after BmNPV infection, we focused on that acetylation of BmAtg8 K13 was changed upon virus challenge. Subsequently, anti-BmAtg8 antibody was generated, and EBSS-induced BmN cellular autophagy model was established. Next, by constructing acetylation-mimic K13Q or deacetylation-mimic K13R mutant BmAtg8, we further examined that K13 of BmAtg8 was acetylated after BmNPV infection and chose 3 h as an appropriate point after EBSS treatment for autophagy initiation. Furthermore, acetylation of BmAtg8 K13 significantly reduced BmAtg8-PE formation in the presence of EBSS, thereby interfering autophagy initiation. Interestingly, acetylated K13 of BmAtg8 contributed to weaken interaction with Atg7, which may influence BmAtg8-PE conjugation. Eventually, acetylation of BmAtg8 K13 is critical for attenuating cell rescue through impaired autophagy initiation. Taken together, our data support an acetylated molecular function for BmAtg8 during starvation-induced autophagy, and provide insights into the modulating mechanisms that potentially reveal the LC3 (a mammalian homolog of Atg8) function in mammal.

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Acknowledgements

This work was supported by the Science foundation of Zhejiang province (No. LY17C170006) and National High-tech R&D program (863 Program) (No. 2011AA100603).

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W.Y conceived and designed the experiments. S.X, F.M and D.H performed the experiments. H.Y, J.L, E.O, Y.Z and Y.Q participated in data analysis and provided technical assistance. W.Y and F.M drafted the manuscript. All authors read and approved the final manuscript.

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Correspondence to Wei Yu.

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Xue, S., Mao, F., Hu, D. et al. Acetylation of BmAtg8 inhibits starvation-induced autophagy initiation. Mol Cell Biochem 457, 73–81 (2019). https://doi.org/10.1007/s11010-019-03513-y

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