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Autophagy. 2017 Jan 2;13(1):187-200. doi: 10.1080/15548627.2016.1254864. Epub 2016 Nov 15.

Ubiquitin-coated nanodiamonds bind to autophagy receptors for entry into the selective autophagy pathway.

Author information

1
a Department and Institute of Biological Science and Technology , National Chiao Tung University , Hsinchu , Taiwan.
2
b Institute of Molecular Medicine and Bioengineering, National Chiao Tung University , Hsinchu , Taiwan.
3
c Department of Chemistry , National Dong Hwa University , Hualien , Taiwan.
4
d Institute of Atomic and Molecular Sciences, Academia Sinica , Taipei , Taiwan.
5
e Institute of Bioinformatics and Systems Biology, National Chiao Tung University , Hsinchu , Taiwan.

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.

KEYWORDS:

autophagy receptors; lysosome; nanodiamonds; selective autophagy; ubiquitin

PMID:
27846374
PMCID:
PMC5240834
DOI:
10.1080/15548627.2016.1254864
[Indexed for MEDLINE]
Free PMC Article

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