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

Author

Listed:
  • Annmary Paul Erinjeri

    (University College London)

  • Xunyan Wang

    (University College London)

  • Rhianna Williams

    (University College London)

  • Riccardo Zenezini Chiozzi

    (University College London
    University College London)

  • Konstantinos Thalassinos

    (University College London
    University College London
    University of London)

  • Johnathan Labbadia

    (University College London)

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.

Suggested Citation

  • Annmary Paul Erinjeri & Xunyan Wang & Rhianna Williams & Riccardo Zenezini Chiozzi & Konstantinos Thalassinos & Johnathan Labbadia, 2024. "HSF-1 promotes longevity through ubiquilin-1-dependent mitochondrial network remodelling," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54136-x
    DOI: 10.1038/s41467-024-54136-x
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