Interaction of bile acids with functionally active liver mitochondria: uncoupling activity, detergent effect, and...

Area of Science:

• Mitochondrial biochemistry
• Cellular metabolism
• Lipid biochemistry

Background:

• Bile acids are crucial for digestion and signaling.
• Their direct impact on mitochondrial function, including uncoupling and antioxidant effects, requires quantitative investigation.

Purpose of the Study:

• To investigate the interactions of primary and secondary bile acids with isolated rat liver mitochondria.
• To quantify bile acid uncoupling activity, detergent effects, and antioxidant properties.
• To correlate these effects with bile acid lipophilicity and structure.

Main Methods:

• Quantification of bile acid partitioning using the effective distribution coefficient.
• Assessment of mitochondrial respiration (state 4, ADP/O ratio, respiratory control ratio) and electron transport chain activity.
• Measurement of mitochondrial hydrogen peroxide (H2O2) generation.

Main Results:

• Uncoupling potency correlated with lipophilicity: LCA > CDCA > CA; UDCA showed significantly lower activity.
• Bile acids induced mild uncoupling via a protonophoric mechanism, reducing ADP/O and respiratory control ratios.
• Bile acids exhibited mild detergent effects, increasing NADH-stimulated respiration, with UDCA and CA being most effective.
• At uncoupling concentrations, all bile acids suppressed mitochondrial H2O2 generation by 30-40%.

Conclusions:

• Bile acids possess dual roles in modulating mitochondrial function, acting as protonophores and antioxidants.
• Structure-dependent lipophilicity dictates bile acid uncoupling potency.
• These findings offer quantitative insights into bile acid-mitochondria interactions and their physiological relevance.