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Nerolidol effects on mitochondrial and cellular energetics.

Fernanda M Ferreira1, Carlos M Palmeira, Maria M Oliveira

  • 1CERNAS, Department of Environment, Agricultural College of Coimbra, Coimbra, Portugal.

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Nerolidol, a plant compound, disrupts cellular energy production by affecting ATP synthase in mitochondria. This leads to decreased energy levels, cell death, and growth arrest in liver cancer cells.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Toxicology

Background:

  • Nerolidol is a sesquiterpenoid found in various plant essential oils.
  • Its effects on cellular and mitochondrial energetics are not fully understood.

Purpose of the Study:

  • To investigate the toxic effects of nerolidol on mitochondrial and cellular energy metabolism.
  • To explore the impact of nerolidol on cell viability and growth in a liver cancer cell line.

Main Methods:

  • Experiments were conducted using rat liver mitochondria and the human hepatocellular liver carcinoma cell line (HepG2).
  • Assays measured mitochondrial phosphorylative system activity, respiratory chain activity, ATP/ADP levels, and mitochondrial transmembrane electric potential.
  • Cell death and growth arrest were assessed in HepG2 cells exposed to nerolidol.

Main Results:

  • Nerolidol decreased the phosphorylative system activity of rat liver mitochondria, indicating a direct effect on F1-ATPase, and reduced the respiratory control ratio.
  • Cellular ATP/ADP levels decreased in a concentration-dependent manner, suggesting an impact on F(0)F(1)-ATP synthase.
  • Nerolidol delayed mitochondrial permeability transition, potentially due to antioxidant activity, and decreased mitochondrial transmembrane electric potential.
  • In HepG2 cells, nerolidol induced cell death and growth arrest, correlating with reduced bioenergetic efficiency.

Conclusions:

  • Nerolidol directly affects mitochondrial ATP synthase, leading to impaired cellular energy production.
  • The observed decrease in bioenergetic efficiency contributes to nerolidol-induced cytotoxicity and growth inhibition in liver cancer cells.