The Drosophila bang-sensitive mutant tko25t, manifesting a global deficiency in oxidative phosphorylation due to a mitochondrial protein synthesis defect, exhibits a pronounced delay in larval development. We previously identified a number of metabolic abnormalities in tko25t larvae, including elevated pyruvate and lactate, and found the larval gut to be a crucial tissue for the regulation of larval growth in the mutant. Here we established that expression of wild-type tko in any of several other tissues of tko25t also partially alleviates developmental delay. The effects appeared to be additive, whilst knockdown of tko in a variety of specific tissues phenocopied tko25t, producing developmental delay and bang-sensitivity. These findings imply the existence of a systemic signal regulating growth in response to mitochondrial dysfunction. Drugs and RNAi-targeted on pyruvate metabolism interacted with tko25t in ways that implicated pyruvate or one of its metabolic derivatives in playing a central role in generating such a signal. RNA-seq revealed that dietary pyruvate-induced changes in transcript representation were mostly non-coherent with those produced by tko25t or high-sugar, consistent with the idea that growth regulation operates primarily at the translational and/or metabolic level.

中文翻译：

---

线粒体功能障碍产生与果蝇幼虫丙酮酸有关的生长受限信号。

果蝇爆炸敏感的突变体tko25t，由于线粒体蛋白质合成缺陷，显示出氧化磷酸化的整体缺陷，在幼虫发育中表现出明显的延迟。我们以前在tko25t幼虫中发现了许多代谢异常，包括丙酮酸和乳酸盐升高，并发现幼虫肠道是调节突变体中幼虫生长的关键组织。在这里，我们确定野生型tko在tko25t的其他几种组织中的表达也可以部分缓解发育延迟。这种作用似乎是累加的，而在特异复制tko25t的多种特定组织中敲除tko会产生发育延迟和爆炸敏感性。这些发现暗示存在响应线粒体功能障碍而调节生长的系统性信号。靶向丙酮酸代谢的药物和RNAi与tko25t相互作用，这暗示丙酮酸或其代谢衍生物之一在产生此类信号中起着核心作用。RNA-seq显示，饮食中丙酮酸引起的转录本表达变化与tko25t或高糖所产生的变化大部分不一致，这与生长调节主要在翻译和/或代谢水平上起作用的想法一致。