20-hydroxyecdysone Upregulates Atg Genes to Induce Autophagy in Bombyx Fat Body

Autophagy is a ubiquitous event in eukaryotes and mediates a highly regulated self-degradation process that is initiated as an adaptive response in unfavorable conditions, such as nutrient deprivation. During autophagy, unnecessary organelles and dysfunctional proteins are sequestered into autophagosomes and finally delivered to lysosomes for degradation.

Researchers led by Dr. LI Sheng from the Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences reported that the insect molting hormone, 20-hydroxyecdysone (20E), upregulates the autophagy related (Atg) genes to induce autophagy in the fat body of the silkworm, Bombyx mori.

In the Bombyx fat body, autophagy occurs and Atg gene expression peaks during the non-feeding molting and pupation stages when 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 (EcRDN) 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 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.

Based on the above results, they conclude that in addition to blocking TORC1 activity for autophagosome initiation, 20E upregulates Atg genes to induce autophagy in the Bombyx fat body. A model of “upstream-gate/flow-downstream” has been proposed. Importantly, this study provides the Bombyx fat body as an excellent system to study autophagy.

Entitled “20-hydroxyecdysone upregulates Atg genes to induce autophagy in the Bombyx fat body”, this research was published online in Autophagy on May 14, 2013. This work was carried out by Dr. TIAN Ling and colleagues, under the supervision of Prof. LI Sheng, and supported by National Basic Research Program of China and the Natural Science Foundation of China.

A: Reduction of autophagy by RNAi knockdown of Atg1 and USP
B: Identification of an EcRE in the Atg1 promoter region
C: A model of “upstream-gate/flow-downstream” for 20E-induced autophagy