Zhang Jie, Liu Suning, Li Yang, Xu Guanfeng, Deng Huimin, King-Jones Kirst, Li Sheng
Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Guangzhou Key Laboratory of Insect Development Regulation and Application Research, Institute of Insect Science and Technology & School of Life Sciences, South China Normal University, Guangzhou, China.
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Nat Commun. 2025 Feb 1;16(1):1258. doi: 10.1038/s41467-025-56528-z.
Steroid hormones are powerful endocrine regulators, but little is known about how environmental conditions modulate steroidogenesis to reprogram developmental fates. Here, we use the Drosophila prothoracic gland (PG) to investigate how a nutrient restriction checkpoint (NRC) ensures or blocks developmental progression and sexual maturation via regulating steroidogenesis. Extensive transcriptome analysis of the PG reveals that pre-NRC starvation significantly downregulates mitochondria-associated genes. Pre-NRC starvation reduces prothoracicotropic neuropeptide hormone signaling, insulin signaling, and TORC1 activity in PG cells, which prevent mitochondrial fragmentation and import of Disembodied, a key steroidogenic enzyme. Ultimately, pre-NRC starvation causes severe mitophagy and proteasome dysfunction, blocking steroidogenesis and metamorphosis. By contrast, post-NRC starvation does not impair mitochondrial homeostasis in PG cells but reduces sit expression and induces moderate autophagy to promote steroidogenesis, leading to precocious metamorphosis. This study constitutes a paradigm for exploring how steroid hormone levels are controlled in response to environmental stress during developmental checkpoints.
类固醇激素是强大的内分泌调节因子，但对于环境条件如何调节类固醇生成以重新编程发育命运，我们知之甚少。在这里，我们利用果蝇前胸腺（PG）来研究营养限制检查点（NRC）如何通过调节类固醇生成来确保或阻断发育进程和性成熟。对PG进行的广泛转录组分析表明，NRC前饥饿显著下调与线粒体相关的基因。NRC前饥饿会降低PG细胞中促前胸腺激素神经肽信号传导、胰岛素信号传导和TORC1活性，从而阻止线粒体碎片化以及关键类固醇生成酶“无实体”的导入。最终，NRC前饥饿会导致严重的线粒体自噬和蛋白酶体功能障碍，阻断类固醇生成和变态发育。相比之下，NRC后饥饿不会损害PG细胞中的线粒体稳态，但会降低sit表达并诱导适度自噬以促进类固醇生成，从而导致早熟变态。这项研究为探索在发育检查点期间如何响应环境压力来控制类固醇激素水平提供了一个范例。
