2024年8月26日 / 最終更新日 : 2024年8月26日 ad_y ニュース

2024年 新着論文 43　細胞情報学分野から論文が発表されました

The Rubicon-WIPI axis regulates exosome biogenesis during ageing

Nat Cell Biol. 2024 Aug 22. doi: 10.1038/s41556-024-01481-0. Online ahead of print.

Authors

Kyosuke Yanagawa  1   2 , Akiko Kuma  1   3 , Maho Hamasaki  1   4 , Shunbun Kita  5   6 , Tadashi Yamamuro  7 , Kohei Nishino  8 , Shuhei Nakamura  1   4   9   10 , Hiroko Omori  11 , Tatsuya Kaminishi  1   12 , Satoshi Oikawa  7   13 , Yoshio Kato  14 , Ryuya Edahiro  15   16 , Ryosuke Kawagoe  17 , Takako Taniguchi  17 , Yoko Tanaka  18 , Takayuki Shima  1   10 , Keisuke Tabata  1   4 , Miki Iwatani  1 , Nao Bekku  1 , Rikinari Hanayama  19   20 , Yukinori Okada  15   21   22   23   24 , Takayuki Akimoto  25 , Hidetaka Kosako  8 , Akiko Takahashi  18 , Iichiro Shimomura  5 , Yasushi Sakata  2 , Tamotsu Yoshimori  26   27   28   29

Affiliations

  • 1 Department of Genetics, Graduate School of Medicine, Osaka University, Suita, Japan.
  • 2 Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
  • 3 Health Promotion System Science, Graduate School of Medicine, Osaka University, Suita, Japan.
  • 4 Laboratory of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
  • 5 Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
  • 6 Tokyo New Drug Research Laboratories, Pharmaceutical Business Unit, Kowa Company, Higashimurayama, Japan.
  • 7 Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
  • 8 Division of Cell Signaling, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
  • 9 Institute for Advanced Co-Creation Studies, Osaka University, Suita, Japan.
  • 10 Department of Biochemistry, Nara Medical University, Kashihara, Japan.
  • 11 Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • 12 Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan.
  • 13 Waseda Institute for Sport Sciences, Waseda University, Tokorozawa, Japan.
  • 14 Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
  • 15 Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • 16 Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan.
  • 17 i2i-Labo, Yokohama Research Center, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Yokohama, Japan.
  • 18 Division of Cellular Senescence, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
  • 19 Department of Immunology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
  • 20 WPI Nano Life Science Institute, Kanazawa University, Kanazawa, Japan.
  • 21 Department of Genome Informatics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • 22 Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • 23 Laboratory of Statistical Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • 24 WPI Premium Research Institute for Human Metaverse Medicine, Osaka University, Suita, Japan.
  • 25 Laboratory of Muscle Biology, Faculty of Sport Sciences, Waseda University, Tokorozawa, Japan.
  • 26 Department of Genetics, Graduate School of Medicine, Osaka University, Suita, Japan. tamotsu.yoshimori@gmail.com.
  • 27 Health Promotion System Science, Graduate School of Medicine, Osaka University, Suita, Japan. tamotsu.yoshimori@gmail.com.
  • 28 Laboratory of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan. tamotsu.yoshimori@gmail.com.
  • 29 Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan. tamotsu.yoshimori@gmail.com.

Abstract

Cells release intraluminal vesicles in multivesicular bodies as exosomes to communicate with other cells. Although recent studies suggest an intimate link between exosome biogenesis and autophagy, the detailed mechanism is not fully understood. Here we employed comprehensive RNA interference screening for autophagy-related factors and discovered that Rubicon, a negative regulator of autophagy, is essential for exosome release. Rubicon recruits WIPI2d to endosomes to promote exosome biogenesis. Interactome analysis of WIPI2d identified the ESCRT components that are required for intraluminal vesicle formation. Notably, we found that Rubicon is required for an age-dependent increase of exosome release in mice. In addition, small RNA sequencing of serum exosomes revealed that Rubicon determines the fate of exosomal microRNAs associated with cellular senescence and longevity pathways. Taken together, our current results suggest that the Rubicon-WIPI axis functions as a key regulator of exosome biogenesis and is responsible for age-dependent changes in exosome quantity and quality.

© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
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