Fig. 5. Coordination of proteostasis and ribosome dynamics regulates life span modulated by XPO-1.

Inhibition of XPO-1 causes repartitioning of key proteins involved in mRNA functions, proteostasis, and ribosomal proteins to the nucleus. A concomitant reduction of nucleolar size is mediated by reduced levels of nucleolar protein FIB-1 and turnover of ribosomal subunit protein RPL-11 via its association with autophagy protein LGG-1. Protein redistribution and nucleolar constriction lead to enhanced proteostasis, global translation reduction, and altered translatome, ultimately enhancing longevity.