RRC ID 50403
Author Takahashi A, Okada R, Nagao K, Kawamata Y, Hanyu A, Yoshimoto S, Takasugi M, Watanabe S, Kanemaki MT, Obuse C, Hara E.
Title Exosomes maintain cellular homeostasis by excreting harmful DNA from cells.
Journal Nat Commun
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.
Volume 8
Pages 15287
Published 2017-5-16
DOI 10.1038/ncomms15287
PII ncomms15287
PMID 28508895
PMC PMC5440838
MeSH Animals Apoptosis Cell Cycle Checkpoints Cell Line Cell Line, Tumor Cells, Cultured Cytoplasm / genetics Cytoplasm / metabolism* DNA / metabolism* Exosomes / metabolism* HEK293 Cells HeLa Cells Homeostasis* Humans Mice Models, Biological Reactive Oxygen Species / metabolism
IF 12.121
Times Cited 171
DNA material MarX-puro-FLAG-Dnase2 (RDB15793)