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 and cytochrome c (Cyt. c) release from mitochondria on mitochondria energetic status was investigated. Results of test the PTP opening and Cyt. c release of isolated rat liver mitochondria with different mitochondrial respiratory substrates, electron transport inhibitors and uncoupler by spectrophotometry and western blotting showed that, Cyt. c release from mitochondria by PTP opening. PTP opening and Cyt. c release showed more sensitive and responsive with FADH-linked succinate than with NADH-linked glutamate plus malate as substrate. Partial or full inhibition of electron flow with electron flow inhibitors resulted in partial or full inhibition of PTP opening and Cyt. c release, respectively. Partial recovery of electron flow with electron sponsors resulted in partial recovery of PTP opening and Cyt. c release. PTP opening and Cyt. c release were completely interrupted by uncoupler. These results indicated PTP opening and Cyt. c release are characterized by respiratory substrate selectivity, electron flow dependence and energy coupling reliance. Hence, PTP opening and Cyt. c release tightly depend on mitochondria 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.