HSF-1 Promotes Longevity Through Ubiquilin-1-dependent Mitochondrial Network Remodelling

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Nov 12

PMID 39532882

Authors

Annmary Paul Erinjeri

Xunyan Wang

Rhianna Williams

Riccardo Zenezini Chiozzi

Konstantinos Thalassinos

Johnathan Labbadia

Affiliations

Soon will be listed here.

Abstract

Increased activity of the heat shock factor, HSF-1, suppresses proteotoxicity and enhances longevity. However, the precise mechanisms by which HSF-1 promotes lifespan are unclear. Using an RNAi screen, we identify ubiquilin-1 (ubql-1) as an essential mediator of lifespan extension in worms overexpressing hsf-1. We find that hsf-1 overexpression leads to transcriptional downregulation of all components of the CDC-48-UFD-1-NPL-4 complex, which is central to both endoplasmic reticulum and mitochondria associated protein degradation, and that this is complemented by UBQL-1-dependent turnover of NPL-4.1. As a consequence, mitochondrial network dynamics are altered, leading to increased lifespan. Together, our data establish that HSF-1 mediates lifespan extension through mitochondrial network adaptations that occur in response to down-tuning of components associated with organellar protein degradation pathways.

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