Compounds classified as benzoylphenylurea (BPU), such as diflubenzuron (DFB), are used as insecticides. Although BPU disrupts molting by inhibiting chitin biosynthesis and exhibits insecticidal activity, their exact mode of action remains unknown. Since epidermal cells proliferate and morphologically change from squamous to columnar cells during the early stages of insect molting, we speculate that a transition similar to that from epithelium to mesenchyme occurs and that BPU may inhibit this transition. Here, we addressed this possibility. We found that DFB decreases actin expression in insect cells (the tissue cultures of insect integument). Detailed analysis in Schneider S2 cells reveals that DFB inhibits the expression of actin isoforms (Act5C and Act42A) and the Drosophila ortholog of myocardin-related transcription factor (Mrtf), leading to cell growth suppression. Proteomics identified the Drosophila ortholog of prohibitin (Phb1D and Phb2E) as one of the DFB-binding proteins. DFB inhibits the interaction between Phb1D and Phb2E and induces mitochondrial dysfunction. The knock-down of Phb2E suppresses the expression of Act5C, Act42A, and Mrtf, leading to cell growth inhibition. Thus, the disruption of Phb function is a possible novel target of DFB.

中文翻译：

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除虫脲作为线粒体功能抑制剂的新能力

归类为苯甲酰基苯基脲 (BPU) 的化合物，如除虫脲 (DFB)，被用作杀虫剂。尽管 BPU 通过抑制几丁质生物合成来破坏蜕皮并表现出杀虫活性，但其确切的作用方式仍然未知。由于在昆虫蜕皮的早期阶段，表皮细胞增殖并形态从鳞状细胞转变为柱状细胞，我们推测发生了类似于从上皮细胞到间质细胞的转变，并且BPU可能抑制这种转变。在这里，我们解决了这种可能性。我们发现 DFB 降低了昆虫细胞（昆虫体皮的组织培养物）中肌动蛋白的表达。对 Schneider S2 细胞的详细分析表明，DFB 抑制肌动蛋白异构体（Act5C 和 Act42A）和心肌素相关转录因子 (Mrtf) 的果蝇直系同源物的表达，从而导致细胞生长抑制。蛋白质组学鉴定果蝇抑制素直系同源物（Phb1D 和 Phb2E）是 DFB 结合蛋白之一。DFB 抑制 Phb1D 和 Phb2E 之间的相互作用并诱导线粒体功能障碍。Phb2E 的敲低会抑制 Act5C、Act42A 和 Mrtf 的表达，从而导致细胞生长受到抑制。因此，破坏 Phb 功能是 DFB 可能的新目标。