Dependence of permeability transition pore opening and cytochrome C release from mitochondria on mitochondria energetic status

The dependence of Ca2+-induced permeability transition pore (PTP) opening a nd cytochrome c (Cyt. c) release from mitochondria on mitochondria energeti c status was investigated. Results of test the PTP opening and Cyt. c relea se of isolated rat liver mitochondria with different mitochondrial respirat ory substrates, electron transport inhibitors and uncoupler by spectrophoto metry and western blotting showed that, Cyt. c release from mitochondria by PTP opening. PTP opening and Cyt. c release showed more sensitive and resp onsive with FADH-linked succinate than with NADH-linked glutamate plus mala te as substrate. Partial or full inhibition of electron flow with electron flow inhibitors resulted in partial or full inhibition of PTP opening and C yt. c release, respectively. Partial recovery of electron flow with electro n sponsors resulted in partial recovery of PTP opening and Cyt. c release. PTP opening and Cyt. c release were completely interrupted by uncoupler. Th ese results indicated PTP opening and Cyt. c release are characterized by r espiratory substrate selectivity, electron flow dependence and energy coupl ing reliance. Hence, PTP opening and Cyt. c release tightly depend on mitoc hondria energetic status. These findings suggested also that it is possible to regulate apoptosis by altering mitochondrial energetic status to alter PTP opening and Cyt. c release.