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Exosomes maintain cellular homeostasis by excreting harmful DNA from cells

Author

Listed:
  • 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)
    LSI Medience Corporation)

  • 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
    PRESTO, Japan Science and Technology Agency (JST))

  • Chikashi Obuse

    (Graduate School of Life Science, Hokkaido University)

  • Eiji Hara

    (The Cancer Institute, Japanese Foundation for Cancer Research (JFCR)
    Research Institute for Microbial Diseases (RIMD), Osaka University
    CREST, Japan Agency for Medical Research and Development (AMED))

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.

Suggested Citation

  • Akiko Takahashi & Ryo Okada & Koji Nagao & Yuka Kawamata & Aki Hanyu & Shin Yoshimoto & Masaki Takasugi & Sugiko Watanabe & Masato T Kanemaki & Chikashi Obuse & Eiji Hara, 2017. "Exosomes maintain cellular homeostasis by excreting harmful DNA from cells," Nature Communications, Nature, vol. 8(1), pages 1-16, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15287
    DOI: 10.1038/ncomms15287
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    Cited by:

    1. Nanase Igarashi & Kenichi Miyata & Tze Mun Loo & Masatomo Chiba & Aki Hanyu & Mika Nishio & Hiroko Kawasaki & Hao Zheng & Shinya Toyokuni & Shunsuke Kon & Keiji Moriyama & Yasuyuki Fujita & Akiko Taka, 2022. "Hepatocyte growth factor derived from senescent cells attenuates cell competition-induced apical elimination of oncogenic cells," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Mwikali Kioko & Alena Pance & Shaban Mwangi & David Goulding & Alison Kemp & Martin Rono & Lynette Isabella Ochola-Oyier & Pete C. Bull & Philip Bejon & Julian C. Rayner & Abdirahman I. Abdi, 2023. "Extracellular vesicles could be a putative posttranscriptional regulatory mechanism that shapes intracellular RNA levels in Plasmodium falciparum," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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