Lipid metabolites affected by deficient autophagy antagonize the occurrence of autophagy through AMPK signaling in insects

文献类型： 外文期刊

第一作者： Tian, Ling

作者： Tian, Ling;Zhong, Qien;Yang, Yubei;Tian, Ling;Zhong, Qien;Yang, Yubei;Tian, Ling;Zhong, Qien;Yang, Yubei;Wu, Wenmei;Xiao, Yang;Li, Sheng;Li, Kang;Li, Kang

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关键词： Autophagy; Bombyx mori; Drosophila melanogaster; Lipid degradation; Metabolites

期刊名称：BMC BIOLOGY （ 影响因子：4.5； 五年影响因子：5.4 ）

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年卷期： 2025 年 23 卷 1 期

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收录情况： SCI

摘要： BackgroundAutophagy is essential for removing damaged organelles and intracellular materials as well as invasive pathogens. The autophagic degradation of intracellular lipids plays a key role in maintaining cellular homeostasis. However, the mechanism of lipid metabolism regulated by autophagy, as well as whether or how lipid metabolites affect autophagy, remain unclear.ResultsRNAi of the key autophagy-related (Atg) genes, notably Atg1 and Atg8, suppressed autophagy, while overexpression of these Atg genes facilitated lipid degradation in both Bombyx mori and Drosophila melanogaster. In addition, disrupting autophagosome-lysosome fusion by chloroquine treatment inhibited lipid degradation during both metamorphosis and starvation. LC-MS/MS analysis showed that overexpression of DmAtg1:DmAtg13 mainly degraded glycerolipids, while DmAtg1 mutation predominantly accumulated glycerophospholipids. Notably, the significantly upregulated GPs following autophagy blockage, including C24H50NO7P (LPE, 19:0), C25H52NO7P (LPC, 0:0/17:0), C27H56NO7P (LPC, 0:0/19:0), and C28H58NO7P (LPC, 20:0/0:0), exerted a suppressive effect on autophagy occurrence mainly through the downregulation of AMPK signaling.ConclusionsAutophagosome and autolysosome formations are both critical for lipid degradation. Conversely, the metabolites accumulated due to dysfunctional autophagy inhibit autophagy occurrence by downregulation of AMPK signaling, thereby forming a regulatory loop in insects. Collectively, our results provide valuable insights into applications for beneficial insects and pest management, while also present potential chemicals applied on human diseases related to autophagy or lipid metabolism.

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