Fig. 2

Dose-response of isolated mitochondria to bile acid-induced MPT. Mitochondria were isolated and incubated (1 mg protein/ml) with either DCA, DCA + UDCA, PhAsO, PhAsO + UDCA, HDCA, or DCA + HDCA in respiration buffer as described in Materials and Methods. Percent change in MPT was measured by monitoring mitochondrial swelling. (A) Dose-response to DCA. At time zero, 50–200 µM DCA or 80 µM PhAsO was added and mitochondrial swelling was monitored for an additional 5 min. In the coincubation experiments, mitochondria were preincubated with 500 µM UDCA for 5 min. (B) Dose-response to UDCA. At time zero, 200 µM DCA was added and mitochondrial swelling was monitored for an additional 5 min. In the coincubation experiments, mitochondria were pretreated with 100–500 µM UDCA or 500 µM HDCA for 5 min. Values are mean ± standard deviations (S.D.) of at least five different experiments. ^§p < 0.05 from DCA; *p < 0.001 from DCA or PhAsO.