Proximal tubules eliminate endocytosed gold nanoparticles through an organelle-extrusion-mediated self-renewal mechanism
Proximal tubules eliminate endocytosed gold nanoparticles through an organelle-extrusion-mediated self-renewal mechanism
复制标题
DOI：
10.1038/s41565-023-01366-7
复制
发表时间：
2023-04-17
影响因子：
38.3
通讯作者：
Zheng, Jie
中科院分区：
文献类型：
--
作者：
Huang, Yingyu;Yu, Mengxiao;Zheng, Jie
近端小管积极内化和代谢通过肾小球过滤的溶质，但在生命周期中不断受到外来物质的挑战。因此，了解近端小管如何保持健康至关重要。在这里，我们报告了一个以前未被认识到的机制，有丝分裂静止近端肾小管上皮细胞消除金纳米颗粒，内吞，甚至部分转化为大的nanoassemblies内溶酶体/内体。通过挤压类似于5 μ m的气球样挤出物穿过致密的微绒毛，将完整的含金内吞囊泡与线粒体或其他细胞器一起沿着运输到挤出物中，并将挤出物从膜捏到管腔中，近端肾小管上皮细胞在一个月内将>95%的内吞的金纳米颗粒从肾脏重新消除到尿液中。虽然这种细胞器挤出机制代表了一种新的纳米颗粒消除途径，但它不是由金纳米颗粒激活的，而是正常近端肾小管上皮细胞的内在“管家”功能，用于去除不需要的细胞质内容物和自我更新细胞内细胞器，而无需细胞分裂以维持体内稳态。在本文中，作者报告了金纳米颗粒通过一种新描述的消除途径从肾脏近端小管中消除。
Proximal tubules energetically internalize and metabolize solutes filtered through glomeruli but are constantly challenged by foreign substances during the lifespan. Thus, it is critical to understand how proximal tubules stay healthy. Here we report a previously unrecognized mechanism of mitotically quiescent proximal tubular epithelial cells for eliminating gold nanoparticles that were endocytosed and even partially transformed into large nanoassemblies inside lysosomes/endosomes. By squeezing similar to 5 mu m balloon-like extrusions through dense microvilli, transporting intact gold-containing endocytic vesicles into the extrusions along with mitochondria or other organelles and pinching the extrusions off the membranes into the lumen, proximal tubular epithelial cells re-eliminated >95% of endocytosed gold nanoparticles from the kidneys into the urine within a month. While this organelle-extrusion mechanism represents a new nanoparticle-elimination route, it is not activated by the gold nanoparticles but is an intrinsic 'housekeeping' function of normal proximal tubular epithelial cells, used to remove unwanted cytoplasmic contents and self-renew intracellular organelles without cell division to maintain homoeostasis.Understanding the pathways of nanoparticle removal from the body is important for nanomedicine applications and safety. Here the authors report the elimination of gold nanoparticles from the proximal tubules in the kidney via a newly described elimination pathway.