Dietary isothiocyanates modify mitochondrial functions through their electrophilic reaction

Area of Science:

• Biochemistry
• Mitochondrial Biology
• Toxicology

Background:

• Mitochondria are crucial for cellular respiration and energy production.
• Isothiocyanates (ITCs) are compounds with potential biological activities.
• Understanding the mechanisms of mitochondrial dysfunction is vital for toxicology and disease research.

Purpose of the Study:

• To investigate the effects of benzyl isothiocyanate (ITC) and phenyl ITC on mitochondrial respiration.
• To elucidate the mechanism underlying ITC-induced mitochondrial damage.

Main Methods:

• Mitochondrial respiration assays were performed.
• Mitochondrial swelling and cytochrome c release were measured.
• The role of electrophilic reactions and thiol groups was assessed.
• Cyclosporin A was used to investigate pore-dependent pathways.

Main Results:

• Both benzyl ITC and phenyl ITC inhibited mitochondrial respiration.
• Inhibition was dependent on electrophilic reactions.
• ITC exposure caused mitochondrial swelling and cytochrome c release.
• These effects were prevented by cyclosporin A, indicating involvement of the mitochondrial permeability transition pore.

Conclusions:

• Benzyl ITC and phenyl ITC disrupt mitochondrial respiration via electrophilic reactions.
• The mechanism involves the opening of mitochondrial permeability transition pores.
• Critical thiol groups are likely targets for ITC-induced mitochondrial dysfunction.