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Updated: Jun 26, 2026

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro
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Published on: July 17, 2018

Clioquinol induces mitochondrial toxicity in SH-SY5Y neuroblastoma cells by affecting the respiratory chain complex

Masato Katsuyama1, Noriaki Arakawa2, Takeshi Yaoi3

  • 1Radioisotope Center, Kyoto Prefectural University of Medicine, Japan.

FEBS Letters
|March 24, 2025
PubMed

Insights

Clioquinol drug toxicity may stem from mitochondrial damage. This study shows clioquinol disrupts copper chaperones, impairs Complex IV activity, and reduces ATP, leading to neuronal cell death.

Area of Science:

  • Neuroscience
  • Toxicology
  • Cell Biology

Background:

  • Clioquinol is a suspected cause of subacute myelo-optic neuropathy (SMON).
  • The precise mechanisms of clioquinol-induced neurotoxicity remain unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying clioquinol's neurotoxicity.
  • To examine clioquinol's effects on mitochondrial function and neuronal cell viability.

Main Methods:

  • Utilized SH-SY5Y neuroblastoma cells.
  • Assessed the expression of SCO1 and SCO2 copper chaperones.
  • Measured Complex IV (cytochrome c oxidase) assembly and activity.
  • Quantified cellular ATP levels under glucose-free conditions.
  • Investigated OPA1 degradation and CHCHD10/CHCHD2 expression.

Main Results:

  • Clioquinol suppressed SCO1 and SCO2 expression, crucial for mitochondrial Complex IV.
  • Complex IV assembly and activity were significantly inhibited by clioquinol.
  • Cellular ATP levels decreased in clioquinol-treated cells.
  • Clioquinol induced OMA1-dependent OPA1 degradation and reduced CHCHD10/CHCHD2 expression, impacting mitochondrial structure.

Conclusions:

  • Clioquinol-induced mitochondrial dysfunction, including impaired Complex IV activity and ATP depletion, contributes to neuronal cell death.
  • Disruption of mitochondrial protein homeostasis and structure maintenance pathways are key mechanisms of clioquinol toxicity.
Keywords:
CHCHD10OMA1SCO2SMONclioquinolmitochondria

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