Ambigols Uncouple Oxidative Phosphorylation In Vitro

Area of Science:

• Biochemistry
• Microbiology
• Pharmacology

Background:

• Ambigols are natural products from *Symphyonema bifilamentata* with a broad bioactivity spectrum.
• Ambigols A and C are investigated for potential applications, including new antibiotic development.
• The precise mode of action for ambigols remained largely unknown.

Purpose of the Study:

• To elucidate the mode of action of ambigols A and C.
• To investigate the effects of ambigols on cellular bioenergetics.
• To determine if ambigols target membrane potential in prokaryotic and eukaryotic cells.

Main Methods:

• Assessing the effect of ambigols A and C on oxidative phosphorylation in HeLa cells.
• Measuring mitochondrial membrane potential dissipation.
• Quantifying oxygen consumption rates.
• Evaluating the impact on the membrane potential of Gram-negative bacteria.

Main Results:

• Ambigols A and C were identified as uncouplers of oxidative phosphorylation.
• These compounds dissipate the mitochondrial membrane potential in HeLa cells.
• Ambigols A and C increase the oxygen consumption rate in HeLa cells.
• The membrane potential of Gram-negative bacteria is also targeted by ambigols.

Conclusions:

• The broad bioactivity of ambigols is attributed to their uncoupling effect on oxidative phosphorylation.
• Ambigols disrupt the electrochemical membrane potential in both prokaryotic and eukaryotic cells, indicating unspecific uncoupler effects.
• These findings provide a foundation for understanding ambigols' bioactivity and guide future development of ambigol-based therapeutics.