Rubicon regulates exosome secretion via the non-autophagic pathway

Exosomes are small extracellular vesicles (EVs), which have the diameter of 50-150 nm and originate from intralumenal vesicles in multivesicular endosomes (MVBs). Exosomes secreted from donor cells are delivered to recipient cells for transferring of exosome cargos, such as proteins, lipids and nucleic acids. The cargo transfer by exosomes has a pivotal role in cell-to-cell communication for many cellular processes; however, the detailed mechanism remains largely elusive. In our recent study, we found that RUBCN/rubicon regulates exosome secretion through endosomal recruitment of WIPI2, which promotes ESCRT-dependent MVB formation. We further showed that this pathway is essential for age-dependent increasing of exosomes, which transfer the pro-senescent microRNAs, including <i>Mir26a</i> and <i>Mir486a</i>, and accelerate cellular senescence in the recipient cells. Our findings highlight RUBCN's key role in exosome secretion and its impact on cellular senescence, providing insights into its potential contributions to aging.