Proximal tubules eliminate endocytosed gold nanoparticles through an organelle-extrusion-mediated self-renewal mechanism.

Abstract

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.