日本大阪大学Tamotsu Yoshimori研究团队发现，Rubicon–WIPI轴在衰老过程中调节外泌体的生成。该研究于2024年8月22日在线发表于国际一流学术期刊《自然—细胞生物学》。

研究人员采用了全面的自噬相关因子的RNA干扰筛选，发现自噬的负调控因子Rubicon对外泌体的释放至关重要。Rubicon通过将WIPI2d募集到内涵体中来促进外泌体的生成。对WIPI2d的互作组分析确定了腔内小泡形成所需的ESCRT成分。

值得注意的是，研究人员发现Rubicon对于小鼠中与年龄相关的外泌体释放增加是必需的。此外，对血清外泌体的小RNA测序表明，Rubicon决定了与细胞衰老和长寿通路相关的外泌体微RNA的命运。综上所述，这些结果表明Rubicon–WIPI轴作为外泌体生成的关键调节因子，负责与年龄相关的外泌体数量和质量的变化。

据介绍，细胞通过多泡小体释放腔内小泡作为外泌体与其他细胞进行交流。尽管最近的研究表明外泌体生成与自噬之间存在紧密联系，但详细机制尚未完全明了。

附：英文原文

Title: The Rubicon–WIPI axis regulates exosome biogenesis during ageing

Author: Yanagawa, Kyosuke, Kuma, Akiko, Hamasaki, Maho, Kita, Shunbun, Yamamuro, Tadashi, Nishino, Kohei, Nakamura, Shuhei, Omori, Hiroko, Kaminishi, Tatsuya, Oikawa, Satoshi, Kato, Yoshio, Edahiro, Ryuya, Kawagoe, Ryosuke, Taniguchi, Takako, Tanaka, Yoko, Shima, Takayuki, Tabata, Keisuke, Iwatani, Miki, Bekku, Nao, Hanayama, Rikinari, Okada, Yukinori, Akimoto, Takayuki, Kosako, Hidetaka, Takahashi, Akiko, Shimomura, Iichiro, Sakata, Yasushi, Yoshimori, Tamotsu

Issue&Volume: 2024-08-22

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.

DOI: 10.1038/s41556-024-01481-0

Source: https://www.nature.com/articles/s41556-024-01481-0