Chenodeoxycholate is a potent inducer of the permeability transition pore in rat liver mitochondria.


Rolo, A P; Oliveira, P J; Moreno, A J; Palmeira, C M

Publication Year 2001
Journal Bioscience reports
Pages 73-80
Volume 21
Issue 1
PMID 11508696.0
DOI 10.1023/a:1010438202519

Several reports support the concept that bile acids may be cytotoxic during cholestatic disease process by causing mitochondrial dysfunction. Here we report additional data and findings aimed at a better understanding of the involvement of the permeability transition pore (PTP) opening in bile acids toxicity. The mitochondrial PTP is implicated as a mediator of cell injury and death in many situations. In the presence of calcium and phosphate, chenodeoxycholic acid (CDCA) induced a permeability transition in freshly isolated rat liver mitochondria, characterized by membrane depolarization, release of matrix calcium, and osmotic swelling. All these events were blocked by cyclosporine A (CyA) and the calcium uniporter inhibitor ruthenium red (RR). The results suggest that CDCA increases the sensitivity of isolated mitochondria in vitro to the calcium-dependent induction of the PTP.