Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Physics of Life (PoL), Technical University Dresden, Dresden, Germany.
Commun Biol. 2024 Jan 24;7(1):121. doi: 10.1038/s42003-024-05804-7.
Recovery from the quiescent developmental stage called dauer is an essential process in C. elegans and provides an excellent model to understand how metabolic transitions contribute to developmental plasticity. Here we show that cholesterol bound to the small secreted proteins SCL-12 or SCL-13 is sequestered in the gut lumen during the dauer state. Upon recovery from dauer, bound cholesterol undergoes endocytosis into lysosomes of intestinal cells, where SCL-12 and SCL-13 are degraded and cholesterol is released. Free cholesterol activates mTORC1 and is used for the production of dafachronic acids. This leads to promotion of protein synthesis and growth, and a metabolic switch at the transcriptional level. Thus, mobilization of sequestered cholesterol stores is the key event for transition from quiescence to growth, and cholesterol is the major signaling molecule in this process.
从休眠的静止发育阶段恢复是秀丽隐杆线虫中的一个重要过程，它为理解代谢转换如何促进发育可塑性提供了一个很好的模型。在这里，我们表明，与小分泌蛋白 SCL-12 或 SCL-13 结合的胆固醇在 dauer 状态下被隔离在肠道腔中。在从 dauer 中恢复后，结合的胆固醇通过内吞作用进入肠细胞的溶酶体，在那里 SCL-12 和 SCL-13 被降解，胆固醇被释放。游离胆固醇激活 mTORC1，并用于产生 dafachronic 酸。这导致蛋白质合成和生长的促进，以及转录水平的代谢转换。因此，隔离胆固醇储存的动员是从静止到生长的关键事件，胆固醇是这个过程中的主要信号分子。
