Exportin 1 modulates lifespan by regulating nucleolar dynamics via the autophagy protein LGG-1/GABARAP

ABSTRACT: Altered nucleolar and ribosomal dynamics are key hallmarks of aging, but their regulation remains unclear. Building on the knowledge that the conserved nuclear export receptor Exportin 1 (XPO-1/XPO1) modulates proteostasis and lifespan, we systematically analyzed the impact of nuclear export on protein metabolism. Using transcriptomic and subcellular proteomic analyses in nematodes, we demonstrate that XPO-1 modulates the nucleo-cytoplasmic distribution of key proteins involved in nucleolar dynamics and ribosome function, including fibrillarin (FIB-1/FBL) and RPL-11 (RPL11). Silencing XPO-1 led to marked reduction in global translation, which was accompanied by decreased nucleolar size and lower fibrillarin levels. A targeted screen of known proteostatic mediators revealed that the autophagy protein LGG-1/GABARAP modulates nucleolar size by regulating RPL-11 levels, linking specific protein degradation to ribosome metabolism. Altogether, our study reveals that nucleolar size, and consequently lifespan, are regulated by LGG-1/GABARAP via ribosome protein surveillance.

INSTRUMENT(S):

ORGANISM(S): Caenorhabditis Elegans

SUBMITTER: Taewook Kang  

LAB HEAD: Louis R Lapierre

PROVIDER: PXD027230 | Pride | 2026-02-23

REPOSITORIES: Pride