Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

IFN-β production promotes metabolic rewiring and protection against oxidative stress in hepatitis delta virus-infected hepatocyte cultures.

Cell death & disease·2025
Same author

Persistent epigenetic memory of SARS-CoV-2 mRNA vaccination in monocyte-derived macrophages.

Molecular systems biology·2025
Same author

Elimination of virus-like particles reduces protein aggregation and extends replicative lifespan in <i>Saccharomyces cerevisiae</i>.

Proceedings of the National Academy of Sciences of the United States of America·2024
Same author

Nuclear Hsp104 safeguards the dormant translation machinery during quiescence.

Nature communications·2024
Same author

Spatial and single-cell profiling of the metabolome, transcriptome and epigenome of the aging mouse liver.

Nature aging·2023
Same author

Arabidopsis metacaspase MC1 localizes in stress granules, clears protein aggregates, and delays senescence.

The Plant cell·2023

Related Experiment Video

Updated: Jul 31, 2025

Purification of Hsp104, a Protein Disaggregase
07:17

Purification of Hsp104, a Protein Disaggregase

Published on: September 30, 2011

17.4K

Artificial Hsp104-mediated systems for re-localizing protein aggregates.

Arthur Fischbach1,2, Angela Johns3, Kara L Schneider3

  • 1Institute for Biomedicine, Sahlgrenska Academy, Centre for Ageing and Health-AgeCap, University of Gothenburg, Gothenburg, Sweden. arthur.fischbach@age.mpg.de.

Nature Communications
|May 10, 2023
PubMed
Summary

Spatial protein quality control (sPQC) can be manipulated to remove toxic protein aggregates, like mutant huntingtin, from cells. This study shows artificially targeting aggregates protects cells from death, offering new insights into neurodegenerative diseases and aging.

More Related Videos

Isolating Potentiated Hsp104 Variants Using Yeast Proteinopathy Models
08:44

Isolating Potentiated Hsp104 Variants Using Yeast Proteinopathy Models

Published on: November 11, 2014

8.2K
Coupled Assays for Monitoring Protein Refolding in Saccharomyces cerevisiae
13:52

Coupled Assays for Monitoring Protein Refolding in Saccharomyces cerevisiae

Published on: July 9, 2013

10.4K

Related Experiment Videos

Last Updated: Jul 31, 2025

Purification of Hsp104, a Protein Disaggregase
07:17

Purification of Hsp104, a Protein Disaggregase

Published on: September 30, 2011

17.4K
Isolating Potentiated Hsp104 Variants Using Yeast Proteinopathy Models
08:44

Isolating Potentiated Hsp104 Variants Using Yeast Proteinopathy Models

Published on: November 11, 2014

8.2K
Coupled Assays for Monitoring Protein Refolding in Saccharomyces cerevisiae
13:52

Coupled Assays for Monitoring Protein Refolding in Saccharomyces cerevisiae

Published on: July 9, 2013

10.4K

Area of Science:

  • Cell Biology
  • Neuroscience
  • Aging Research

Background:

  • Spatial protein quality control (sPQC) sequesters misfolded proteins into cellular inclusions to mitigate toxicity.
  • The role of sPQC in cellular fitness, neurodegenerative diseases, and aging remains an active area of investigation.
  • Huntington's disease is characterized by aggregates of mutant huntingtin (mHtt).

Purpose of the Study:

  • To develop Hsp100-based systems for artificially targeting protein aggregates to non-canonical locations.
  • To investigate the impact of spatial sequestration of protein aggregates on cellular fitness and survival.
  • To explore the potential of this approach in studying neurodegenerative diseases and aging.

Main Methods:

  • Construction of Hsp100-based systems in budding yeast.
  • Artificial targeting of mutant huntingtin (mHtt) aggregates to daughter cells, eisosomes, and endosomes.
  • Manipulation of endogenous age-associated misfolded protein inclusions.
  • Application of the system in human cells.

Main Results:

  • Artificial targeting of mHtt aggregates to daughter cells and organelles was achieved.
  • Removal of mHtt inclusions from mother cells protected them from cell death, suggesting cytotoxicity.
  • Sequestration of endogenous age-associated misfolded proteins did not significantly impact cell lifespan.
  • The system demonstrated efficacy in manipulating mHtt inclusion formation in human cells.

Conclusions:

  • Artificial spatial sequestration of toxic protein aggregates can protect cells from death.
  • This approach provides a novel tool to study the cytotoxicity of protein aggregates in diseases like Huntington's.
  • The Hsp100-based system offers a potential complementary method for investigating sPQC in aging and neurodegenerative conditions.