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Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue
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Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue

Published on: March 23, 2015

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Direct Analysis of Mitochondrial Damage Caused by Misfolded/Destabilized Proteins

Jannatul Aklima1,2, Sawaros Onchaiya1, Tomonori Saotome1,3

  • 1Division of Biotechnology and Life Sciences, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo 184-8588, Japan.

International Journal of Molecular Sciences
|September 9, 2022
PubMed

Insights

Thermally unstable proteins, not just amyloid fibrils, can damage mitochondria. This study reveals that cytosolic protein misfolding can disrupt mitochondrial integrity, impacting cellular homeostasis.

Area of Science:

  • Cellular Biology
  • Biophysics
  • Biochemistry

Background:

  • Protein quality control is vital for maintaining cellular homeostasis.
  • Misfolded proteins can disrupt cellular functions, but the role of non-amyloidogenic proteins is less understood.
  • Mitochondria are crucial for energy production and cell death pathways.

Purpose of the Study:

  • To investigate the impact of non-amyloidogenic, improperly folded proteins on mitochondrial integrity.
  • To identify common characteristics of toxic misfolded proteins affecting mitochondria.
  • To determine if mitochondrial damage by misfolded proteins is amyloid-specific.

Main Methods:

  • Preparation of wild-type and mutant dengue envelope protein domain 3 with varying biophysical properties.
  • Assessment of mitochondrial membrane integrity using fluorescence microscopy and Western blotting.
  • Analysis of protein oligomer size, molten globule-like properties, and thermal stability.

Main Results:

  • Three out of five tested proteins disrupted both inner and outer mitochondrial membrane integrity.
  • The common characteristic of the toxic proteins was their thermal instability.
  • The wild-type protein and one mutant did not exhibit toxicity towards mitochondria.

Conclusions:

  • Thermally unstable proteins, even without forming amyloid fibrils, can cause cellular damage through direct contact with mitochondria.
  • Mitochondrial damage induced by misfolded proteins is not limited to amyloidogenic pathways.
  • Cytosolic protein misfolding poses a risk to mitochondrial function and cellular homeostasis.
Keywords:
dengue envelope protein domain 3membranemisfolded proteinmitochondriathermal instability

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