The Rubicon-WIPI Axis Regulates Exosome Biogenesis During Ageing

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2024 Aug 22

PMID 39174742

Authors

Kyosuke Yanagawa

Akiko Kuma

Maho Hamasaki

Shunbun Kita

Tadashi Yamamuro

Kohei Nishino

Shuhei Nakamura

Hiroko Omori

Tatsuya Kaminishi

Satoshi Oikawa

Yoshio Kato

Ryuya Edahiro

Ryosuke Kawagoe

Takako Taniguchi

Yoko Tanaka

Takayuki Shima

Keisuke Tabata

Miki Iwatani

Nao Bekku

Rikinari Hanayama

Yukinori Okada

Takayuki Akimoto

Hidetaka Kosako

Akiko Takahashi

Iichiro Shimomura

Yasushi Sakata

Tamotsu Yoshimori

Affiliations

Soon will be listed here.

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.

Citing Articles

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