The mechanisms that govern organelle adaptation and remodelling remain poorly defined. The endo-lysosomal system degrades cargo from various routes, including endocytosis, phagocytosis, and autophagy. For phagocytes, endosomes and lysosomes (endo-lysosomes) are kingpin organelles because they are essential to kill pathogens and process and present antigens. During phagocyte activation, endo-lysosomes undergo a morphological transformation, going from a collection of dozens of globular structures to a tubular network in a process that requires the phosphatidylinositol-3-kinase-AKT-mechanistic target of rapamycin (mTOR) signalling pathway. Here, we show that the endo-lysosomal system undergoes an expansion in volume and holding capacity during phagocyte activation within 2 h of lipopolysaccharides (LPS) stimulation. Endo-lysosomal expansion was paralleled by an increase in lysosomal protein levels, but this was unexpectedly largely independent of the transcription factor EB (TFEB) and transcription factor E3 (TFE3), which are known to scale up lysosome biogenesis. Instead, we demonstrate a hitherto unappreciated mechanism of acute organelle expansion via mTOR Complex 1 (mTORC1)-dependent increase in translation, which appears to be mediated by both S6Ks and 4E-BPs. Moreover, we show that stimulation of RAW 264.7 macrophage cell line with LPS alters translation of a subset but not all of mRNAs encoding endo-lysosomal proteins, thereby suggesting that endo-lysosome expansion is accompanied by functional remodelling. Importantly, mTORC1-dependent increase in translation activity was necessary for efficient and rapid antigen presentation by dendritic cells. Collectively, we identified a previously unknown and functionally relevant mechanism for endo-lysosome expansion that relies on mTORC1-dependent translation to stimulate endo-lysosome biogenesis in response to an infection signal.

中文翻译：

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增强的翻译扩大了溶酶体的内在大小，并在吞噬细胞激活过程中促进了抗原呈递。

控制细胞器适应和重塑的机制仍然定义不清。内溶酶体系统可通过多种途径降解货物，包括内吞，吞噬和自噬。对于吞噬细胞，内体和溶酶体（内溶酶体）是主要的细胞器，因为它们对于杀死病原体以及加工和呈递抗原至关重要。在吞噬细胞激活过程中，内溶酶体经历了形态学转变，从数十个球状结构的集合变为管状网络，而这一过程需要磷脂酰肌醇3-激酶-AKT成为雷帕霉素（mTOR）信号传导途径的机械靶标。在这里，我们显示内溶酶体系统在脂多糖（LPS）刺激2小时内吞噬细胞激活期间经历体积和容纳能力的扩展。内溶酶体的扩张与溶酶体蛋白水平的增加平行，但是出乎意料的是，这很大程度上与转录因子EB（TFEB）和转录因子E3（TFE3）无关，后者已知会增加溶酶体的生物发生。取而代之的是，我们证明了迄今为止通过mTOR Complex 1（mTORC1）依赖性翻译增加的急性细胞器扩展机制，该机制似乎由S6K和4E-BP介导。此外，我们表明，用LPS刺激RAW 264.7巨噬细胞细胞系可改变编码内溶酶体蛋白的一个子集但并非所有mRNA的翻译，从而提示内溶酶体扩增伴随功能性重塑。重要的是，mTORC1依赖性翻译活性的增加对于树突状细胞有效且快速的抗原呈递是必要的。