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Updated: Sep 13, 2025

Assessment of Submitochondrial Protein Localization in Budding Yeast Saccharomyces cerevisiae
08:55

Assessment of Submitochondrial Protein Localization in Budding Yeast Saccharomyces cerevisiae

Published on: July 19, 2021

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Mitochondrial protein aggregates recruit key chaperones and are sequestered in a fission- and fusion-dependent

Laura Ruland1, Marc Sylvester2, Lydia Maus3

  • 1Institute for Biochemistry and Molecular Biology (IBMB), University of Bonn, D-53115 Bonn, Germany.

Journal of Cell Science
|July 30, 2025
PubMed

Insights

Mitochondrial protein aggregates are sequestered into a specialized compartment (IMiQ) in yeast, preventing toxicity. Organelle dynamics, particularly fission, are crucial for this protective mechanism, which involves chaperone neutralization.

Area of Science:

  • Mitochondrial biology
  • Cellular stress response
  • Protein quality control

Background:

  • Mitochondrial aggregates can cause proteotoxicity.
  • A mitochondrial protein quality control compartment (IMiQ) sequesters affected polypeptides.
  • Organelle dynamics influence aggregate management.

Purpose of the Study:

  • To investigate the role of mitochondrial organelle dynamics in the sequestration of protein aggregates.
  • To understand the impact of fusion and fission defects on aggregate handling and cellular stress.

Main Methods:

  • Expression of an aggregation-prone protein in the mitochondrial matrix of yeast.
  • Analysis of fusion-deficient and fission-deficient yeast mutants.
  • Quantitative mass spectrometry to analyze the mitochondrial proteome and protein co-aggregation.
  • Assessment of cellular stress phenotypes.

Main Results:

  • Fusion-deficient cells failed to sequester aggregates in IMiQ, leading to stress sensitivity.
  • Fission-deficient cells showed aggregate neutralization via chaperone shell formation.
  • Quantitative mass spectrometry revealed recruitment of respiratory chain proteins and the protein quality control system (PQC) to aggregates.
  • Hsp70 chaperone family members were prominently associated with aggregates.

Conclusions:

  • Mitochondrial dynamics, especially fission, are essential for effective aggregate sequestration and neutralization.
  • Chaperone-dependent neutralization prevents widespread co-aggregation of endogenous mitochondrial proteins.
  • The IMiQ and chaperone systems work together to mitigate proteotoxicity from mitochondrial aggregates.
Keywords:
Cell biologyChaperoneHsp70MitochondriaProtein aggregationProteostasisYeast

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