HSF-1 promotes longevity through ubiquilin-1-dependent mitochondrial network remodelling.

Annmary Paul Erinjeri, Xunyan Wang, Rhianna Williams, Riccardo Zenezini Chiozzi, Konstantinos Thalassinos, Johnathan Labbadia

Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, Division of Biosciences, University College London, London, UK.Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, Division of Biosciences, University College London, London, UK. · pubmed

Paper

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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Research summary

The paper investigates the role of HSF-1 in promoting longevity through mechanisms involving mitochondrial network remodeling and protein degradation pathways. This focus on the underlying biological processes that contribute to lifespan extension aligns well with longevity research. However, while the findings are solid and contribute to our understanding of the molecular mechanisms of aging, they do not represent a major breakthrough or transformative insights that would significantly advance the field.

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