Research Abstract


Exosomes maintain cellular homeostasis by excreting harmful DNA from cells

2017年5月16日 Nature Communications 8 : 15287 doi: 10.1038/ncomms15287 (2017)


Akiko Takahashi, Ryo Okada, Koji Nagao, Yuka Kawamata, Aki Hanyu, Shin Yoshimoto, Masaki Takasugi, Sugiko Watanabe, Masato T Kanemaki, Chikashi Obuse and Eiji Hara

Corresponding Authors

高橋 暁子
公益財団法人 がん研究会

原 英二
公益財団法人 がん研究会(大阪大学 微生物病研究所)

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.