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Nat Commun. 2017 May 16;8:15287. doi: 10.1038/ncomms15287.

Exosomes maintain cellular homeostasis by excreting harmful DNA from cells.

Author information

1
The Cancer Institute, Japanese Foundation for Cancer Research (JFCR), Koto-ku, Tokyo 135-8550, Japan.
2
Graduate School of Life Science, Hokkaido University, Sapporo, Hokkaido 001-0021, Japan.
3
LSI Medience Corporation, Chiyoda-ku, Tokyo 101-8517, Japan.
4
Department of Molecular Microbiology, Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka 565-0871, Japan.
5
Division of Molecular Cell Engineering, Department of Genetics, National Institute of Genetics, ROIS, SOKENDAI, Mishima, Shizuoka 411-8540, Japan.
6
PRESTO, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan.
7
CREST, Japan Agency for Medical Research and Development (AMED), Chiyoda-ku, Tokyo 100-0004, Japan.

Abstract

Emerging evidence is revealing that exosomes contribute to many aspects of physiology and disease through intercellular communication. However, the biological roles of exosome secretion in exosome-secreting cells have remained largely unexplored. Here we show that exosome secretion plays a crucial role in maintaining cellular homeostasis in exosome-secreting cells. The inhibition of exosome secretion results in the accumulation of nuclear DNA in the cytoplasm, thereby causing the activation of cytoplasmic DNA sensing machinery. This event provokes the innate immune response, leading to reactive oxygen species (ROS)-dependent DNA damage response and thus induce senescence-like cell-cycle arrest or apoptosis in normal human cells. These results, in conjunction with observations that exosomes contain various lengths of chromosomal DNA fragments, indicate that exosome secretion maintains cellular homeostasis by removing harmful cytoplasmic DNA from cells. Together, these findings enhance our understanding of exosome biology, and provide valuable new insights into the control of cellular homeostasis.

PMID:
28508895
PMCID:
PMC5440838
DOI:
10.1038/ncomms15287
[Indexed for MEDLINE]
Free PMC Article

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