Ubiquitin-coated nanodiamonds bind to autophagy receptors for entry into the selective autophagy pathway.
Journal
Autophagy
Journal Volume
13
Journal Issue
1
Start Page
187
End Page
200
ISSN
1554-8635
Date Issued
2017-01-02
Author(s)
Liu, Kuang-Kai
Qiu, Wei-Ru
Naveen Raj, Emmanuel
Liu, Huei-Fang
Huang, Hou-Syun
Lin, Yu-Wei
Chen, Ting-Hua
Chen, Chinpiao
Chang, Huan-Cheng
Hwang, Jenn-Kang
Chao, Jui-I
Abstract
Selective macroautophagy/autophagy plays a pivotal role in the processing of foreign pathogens and cellular components to maintain homeostasis in human cells. To date, numerous studies have demonstrated the uptake of nanoparticles by cells, but their intracellular processing through selective autophagy remains unclear. Here we show that carbon-based nanodiamonds (NDs) coated with ubiquitin (Ub) bind to autophagy receptors (SQSTM1 [sequestosome 1], OPTN [optineurin], and CALCOCO2/NDP52 [calcium binding and coiled-coil domain 2]) and are then linked to MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) for entry into the selective autophagy pathway. NDs are ultimately delivered to lysosomes. Ectopically expressed SQSTM1-green fluorescence protein (GFP) could bind to the Ub-coated NDs. By contrast, the Ub-associated domain mutant of SQSTM1 (ΔUBA)-GFP did not bind to the Ub-coated NDs. Chloroquine, an autophagy inhibitor, prevented the ND-containing autophagosomes from fusing with lysosomes. Furthermore, autophagy receptors OPTN and CALCOCO2/NDP52, involved in the processing of bacteria, were found to be involved in the selective autophagy of NDs. However, ND particles located in the lysosomes of cells did not induce mitotic blockage, senescence, or cell death. Single ND clusters in the lysosomes of cells were observed in the xenografted human lung tumors of nude mice. This study demonstrated for the first time that Ub-coated nanoparticles bind to autophagy receptors for entry into the selective autophagy pathway, facilitating their delivery to lysosomes.
Subjects
autophagy receptors
lysosome
nanodiamonds
selective autophagy
ubiquitin
Type
journal article