Succinylation enables IDE to act as a hub of larval tissue destruction and adult tissue reconstruction during insect metamorphosis

Metamorphosis is an important way for insects to adapt to the environment. In this process, larval tissue destruction regulated by 20-hydroxyecdysone (20E) and adult tissue reconstruction regulated by insulin-like peptides (ILPs) occur simultaneously, but the detailed mechanism is still unclear. Here, the results of succinylome, subcellular localization, and protein interaction analysis show that non-succinylated insulin-degrading enzyme (IDE) localizes in the cytoplasm, binds to insulin-like growth factor 2 (IGF-2-like), and degrades it. When the metamorphosis is initiated, 20E up-regulated carnitine palmitoyltransferase 1A (<i>Cpt1a</i>) through transcription factor Krüppel-like factor 15 (KLF15), thus increasing the level of IDE succinylation on K179. Succinylated IDE translocated from cytoplasm to nucleus, combined with ecdysone receptor to promote 20E signaling pathway, causing larval tissue destruction, while IGF-2-like was released to promote adult tissue proliferation. That is, succinylation alters subcellular localization of IDE so that it can bind to different target proteins and act as a hub of metamorphosis.