title: 20-Hydroxyecdysone upregulates Atg genes to induce autophagy in the Bombyx fat body.
abstract: Autophagy is finely regulated at multiple levels and plays crucial roles in development and disease. In the fat body of the silkworm, Bombyx mori, autophagy occurs and Atg gene expression peaks during the nonfeeding molting and pupation stages when the steroid hormone (20-hydroxyecdysone; 20E) is high. Injection of 20E into the feeding larvae upregulated Atg genes and reduced TORC1 activity resulting in autophagy induction in the fat body. Conversely, RNAi knockdown of the 20E receptor partner (USP) or targeted overexpression of a dominant negative mutant of the 20E receptor (EcR (DN) ) in the larval fat body reduced autophagy and downregulated the Atg genes, confirming the importance of 20E-induction of Atg gene expression during pupation. Moreover, in vitro treatments of the larval fat body with 20E upregulated the Atg genes. Five Atg genes were potentially 20E primary-responsive, and a 20E response element was identified in the Atg1 (ortholog of human ULK1) promoter region. Furthermore, RNAi knockdown of 4 key genes (namely Br-C, E74, HR3 and βftz-F1) in the 20E-triggered transcriptional cascade reduced autophagy and downregulated Atg genes to different levels. Taken together, we conclude that in addition to blocking TORC1 activity for autophagosome initiation, 20E upregulates Atg genes to induce autophagy in the Bombyx fat body.
authors.affiliation: Key Laboratory of Insect Developmental and Evolutionary Biology; Institute of Plant Physiology and Ecology; Shanghai Institutes for Biological Sciences; Chinese Academy of Sciences; Shanghai, China; State Key Laboratory of Silkworm Genome Biology; Southwest University; Chongqing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tian
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Enen
authors.initials: E
authors.lastname: Guo
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Deng
authors.forename: Sanyuan
authors.initials: S
authors.lastname: Ma
authors.forename: Qingyou
authors.initials: Q
authors.lastname: Xia
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D001483:Base Sequence; D012831:Bombyx / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000648:ultrastructure; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004441:Ecdysterone / Q000494:pharmacology*; D005216:Fat Body / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D017344:Genes, Insect / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D034622:RNA Interference / Q000187:drug effects; D020218:Response Elements / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics
chemical_list: D019476:Insect Proteins; D004441:Ecdysterone
keywords: 20-hydroxyecdysone; ATG8; Atg1; Atggenes; Bombyx mori; TORC1; autophagy; fat body; transcriptional regulation