Exosomes maintain cellular homeostasis by excreting harmful DNA from cells

Akiko Takahashi (), Ryo Okada, Koji Nagao, Yuka Kawamata, Aki Hanyu, Shin Yoshimoto, Masaki Takasugi, Sugiko Watanabe, Masato T Kanemaki, Chikashi Obuse and Eiji Hara ()
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Akiko Takahashi: The Cancer Institute, Japanese Foundation for Cancer Research (JFCR)
Ryo Okada: The Cancer Institute, Japanese Foundation for Cancer Research (JFCR)
Koji Nagao: Graduate School of Life Science, Hokkaido University
Yuka Kawamata: The Cancer Institute, Japanese Foundation for Cancer Research (JFCR)
Aki Hanyu: The Cancer Institute, Japanese Foundation for Cancer Research (JFCR)
Shin Yoshimoto: The Cancer Institute, Japanese Foundation for Cancer Research (JFCR)
Masaki Takasugi: Research Institute for Microbial Diseases (RIMD), Osaka University
Sugiko Watanabe: Research Institute for Microbial Diseases (RIMD), Osaka University
Masato T Kanemaki: National Institute of Genetics, ROIS, SOKENDAI
Chikashi Obuse: Graduate School of Life Science, Hokkaido University
Eiji Hara: The Cancer Institute, Japanese Foundation for Cancer Research (JFCR)

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15287

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