Atg1 phosphorylation is activated by AMPK and indispensable for autophagy induction in insects.

Abstract

Phosphorylation is a key post-translational modification in regulating autophagy in yeast and mammalians, yet it is not fully illustrated in invertebrates such as insects. ULK1/Atg1 is a functionally conserved serine/threonine protein kinase involved in autophagosome initiation. As a result of alternative splicing, Atg1 in the silkworm, Bombyx mori, is present as three mRNA isoforms, with BmAtg1c showing the highest expression levels. Here, we found that BmAtg1c mRNA expression, BmAtg1c protein expression and phosphorylation, and autophagy simultaneously peaked in the fat body during larval-pupal metamorphosis. Importantly, two BmAtg1c phosphorylation sites were identified at Ser269 and Ser270, which were activated by BmAMPK, the major energy-sensing kinase, upon stimulation with 20-hydroxyecdysone and starvation; additionally, these Atg1 phosphorylation sites are evolutionarily conserved in insects. The two BmAMPK-activated phosphorylation sites in BmAtg1c were found to be required for BmAMPK-induced autophagy. Moreover, the two corresponding DmAtg1 phosphorylation sites in the fruit fly, Drosophila melanogaster, are functionally conserved for autophagy induction. In conclusion, AMPK-activated Atg1 phosphorylation is indispensable for autophagy induction and evolutionarily conserved in insects, shedding light on how various groups of organisms differentially regulate ULK1/Atg1 phosphorylation for autophagy induction.

• Authors: Haigang Zhao, Shihui Long, Suning Liu, Dongwei Yuan, Danyan Huang, Jing Xu, Qiuqin Ma, Guirong Wang, Jian Wang, Sheng Li, Ling Tian, Kang Li
• Journal: Insect biochemistry and molecular biology (Insect Biochem Mol Biol) Vol. 152 Pg. 103888 (01 2023) ISSN: 1879-0240 [Electronic] England
• PMID: 36493962 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• AMP-Activated Protein Kinases
• Protein Serine-Threonine Kinases
• Atg1 protein, Drosophila
• Autophagy-Related Protein-1 Homolog
• Drosophila Proteins

Topics

• Animals
• Phosphorylation
• AMP-Activated Protein Kinases (genetics, metabolism)
• Drosophila melanogaster (metabolism)
• Protein Serine-Threonine Kinases (genetics, metabolism)
• Drosophila (metabolism)
• Autophagy (genetics)
• Mammals (metabolism)
• Autophagy-Related Protein-1 Homolog (genetics, metabolism)
• Drosophila Proteins (metabolism)