Science advancesJun 24, 2026

FUBL-3/FUBP1 helps change DNA packaging during mitochondrial stress and may influence lifespan

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 25, 2026

Abstract

FUBL-3, a protein linked to human FUBP1, is identified as a key regulator of chromatin remodeling in response to mitochondrial stress.

FUBL-3 translocates to intestinal nuclei during mitochondrial stress, indicating its role in cellular response.
It drives nucleosome remodeling and chromatin condensation, which are crucial for activating the mitochondrial unfolded protein response.
Loss of FUBL-3 disrupts chromatin compaction and prevents lifespan extension under stress conditions.
Overexpression of FUBL-3 restructures chromatin, triggers the unfolded protein response, and extends lifespan.
Human FUBP1 can rescue chromatin remodeling functions in a worm model, suggesting conservation across species.

Simplified

Mitochondrial stress activates nuclear transcriptional programs to restore homeostasis and promote longevity; yet, the nuclear effector that directly reshapes chromatin during stress remains unclear. Through a forward genetic screen in Caenorhabditis elegans, we identify FUBL-3, the homolog of human far-upstream elements binding protein 1 (FUBP1), as a conserved regulator that couples mitochondrial stress to chromatin remodeling. FUBL-3 translocates to intestinal nuclei upon stress, where it drives nucleosome remodeling and deacetylase-dependent chromatin condensation and activates mitochondrial unfolded protein response (UPR^mt). Loss of fubl-3 disrupts chromatin compaction and abolishes stress-induced lifespan extension, while its overexpression is sufficient to restructure chromatin, trigger UPR^mt, and extend lifespan. Notably, human FUBP1 rescues fubl-3 mutants in worms and mediates chromatin remodeling in mammalian cells under mitochondrial stress. FUBP1 binds promoters of proteostasis and mitochondrial quality control genes, supporting its role in nuclear adaptation. Our study identifies FUBL-3/FUBP1 as a conserved mitochondrial-to-nuclear communicator that reprograms chromatin architecture to promote stress resilience and healthy aging.