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Microthermal-induced subcellular-targeted protein damage in cells on plasmonic nanosilver-modified surfaces evokes a two-phase HSP-p97/VCP response

Author

Listed:
  • Martin Mistrik

    (Palacky University)

  • Zdenek Skrott

    (Palacky University)

  • Petr Muller

    (Masaryk Memorial Cancer Institute)

  • Ales Panacek

    (Palacky University)

  • Lucie Hochvaldova

    (Palacky University)

  • Katarina Chroma

    (Palacky University)

  • Tereza Buchtova

    (Palacky University)

  • Veronika Vandova

    (Masaryk Memorial Cancer Institute)

  • Libor Kvitek

    (Palacky University)

  • Jiri Bartek

    (Palacky University
    Danish Cancer Society Research Center
    Karolinska Institute)

Abstract

Despite proteotoxic stress and heat shock being implicated in diverse pathologies, currently no methodology to inflict defined, subcellular thermal damage exists. Here, we present such a single-cell method compatible with laser-scanning microscopes, adopting the plasmon resonance principle. Dose-defined heat causes protein damage in subcellular compartments, rapid heat-shock chaperone recruitment, and ensuing engagement of the ubiquitin–proteasome system, providing unprecedented insights into the spatiotemporal response to thermal damage relevant for degenerative diseases, with broad applicability in biomedicine. Using this versatile method, we discover that HSP70 chaperone and its interactors are recruited to sites of thermally damaged proteins within seconds, and we report here mechanistically important determinants of such HSP70 recruitment. Finally, we demonstrate a so-far unsuspected involvement of p97(VCP) translocase in the processing of heat-damaged proteins. Overall, we report an approach to inflict targeted thermal protein damage and its application to elucidate cellular stress-response pathways that are emerging as promising therapeutic targets.

Suggested Citation

  • Martin Mistrik & Zdenek Skrott & Petr Muller & Ales Panacek & Lucie Hochvaldova & Katarina Chroma & Tereza Buchtova & Veronika Vandova & Libor Kvitek & Jiri Bartek, 2021. "Microthermal-induced subcellular-targeted protein damage in cells on plasmonic nanosilver-modified surfaces evokes a two-phase HSP-p97/VCP response," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-20989-9
    DOI: 10.1038/s41467-021-20989-9
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