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.
Huang
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X
National Laboratory of Biomacromolecules, Institute of Biophysics, Academia Sinica, Beijing, China.
Zhai
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D
Huang
Y
Y
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000494:pharmacology; D019069:Cell Respiration; D003574:Cytochrome c Group / Q000378:metabolism*; D004579:Electron Transport; D004734:Energy Metabolism; D005260:Female; D007473:Ion Channels; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010539:Permeability; D051381:Rats; D013997:Time Factors
D003574:Cytochrome c Group; D007473:Ion Channels; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D002118:Calcium