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 ~5 µm 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.

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，了解近端肾小管如何保持健康至关重要。在这里，我们报告了一种以前未被认识的有丝分裂静止的近端肾小管上皮细胞的机制，用于消除被内吞甚至部分转化为溶酶体/内体内的大型纳米组件的金纳米粒子。通过挤压 ~5 µm 气球状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运输到挤出物中，并将挤出物从膜上夹入管腔，近端肾小管上皮细胞被重新消除 >95%一个月内将金纳米粒子从肾脏内吞到尿液中。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，但它不会被金纳米颗粒激活，而是正常近端肾小管上皮细胞的固有“管家”功能，用于去除不需要的细胞质内容物并自我更新细胞内细胞器，而无需细胞分裂以维持体内平衡。