Silver Ion Induces a Cyclosporine A-Insensitive Permeability Transition in Rat Liver Mitochondria and Release of Apoptogenic Cytochrome c

2003 ◽  
Vol 134 (1) ◽  
pp. 43-49 ◽  
Author(s):  
M. R. Almofti
Keyword(s):  
Cytochrome C ◽  
Rat Liver ◽  
Cyclosporine A ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Silver Ion ◽  
Rat Liver Mitochondria

Role of calcium and superoxide dismutase in sensitizing mitochondria to peroxynitrite-induced permeability transition

2004 ◽  
Vol 286 (1) ◽  
pp. H39-H46 ◽  
Author(s):  
Paul S. Brookes ◽  
Victor M. Darley-Usmar
Keyword(s):  
Superoxide Dismutase ◽  
Cytochrome C ◽  
Rat Liver ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Isolated Rat Liver ◽  
Ptp Opening ◽  
Isolated Rat

The mitochondrial permeability transition pore (PTP) is a membrane protein complex assembled and opened in response to Ca2+ and oxidants such as peroxynitrite (ONOO–). Opening the PTP is mechanistically linked to the release of cytochrome c, which participates in downstream apoptotic signaling. However, the molecular basis of the synergistic interactions between oxidants and Ca2+ in promoting the PTP are poorly understood and are addressed in the present study. In isolated rat liver mitochondria, it was found that the timing of the exposure of the isolated rat liver mitochondria to Ca2+ was a critical factor in determining the impact of ONOO– on PTP. Specifically, addition of Ca2+ alone, or ONOO– and then Ca2+, elicited similar low levels of PTP opening, whereas ONOO– alone was ineffective. In contrast, addition of Ca2+ and then ONOO– induced extensive PTP opening and cytochrome c release. Interestingly, Cu/Zn-superoxide dismutase enhanced pore opening through a mechanism independent of its catalytic activity. These data are consistent with a model in which Ca2+ reveals a molecular target that is now reactive with ONOO–. As a test of this hypothesis, tyrosine nitration was determined in mitochondria exposed to ONOO– alone or to Ca2+ and then ONOO–, and mitochondrial membrane proteins were analyzed using proteomics. These studies suggest protein targets revealed by Ca2+ include dehydrogenases and CoA-containing enzymes. These data are discussed in the context of the role of mitochondria, Ca2+, and ONOO– in apoptotic signaling.

scholarly journals Cytochrome c release from isolated rat liver mitochondria can occur independently of outer-membrane rupture: possible role of contact sites

2000 ◽  
Vol 348 (2) ◽  
pp. 343-350 ◽  
Author(s):  
Elena DORAN ◽  
Andrew P. HALESTRAP
Keyword(s):  
Cytochrome C ◽  
Rat Liver ◽  
Adenine Nucleotide ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Voltage Dependent Anion Channel ◽  
Cytochrome C Release ◽  
Membrane Rupture ◽  
Contact Sites

Percoll-purified rat liver mitochondria were shown to contain BAX dimer and rapidly (< 2 min) release 5-10% of their cytochrome c when incubated in a standard KCl incubation medium under energized conditions. This release was not accompanied by release of adenylate kinase (AK), another intermembrane protein, and was not inhibited by Mg2+, dATP, inhibitors of the permeability transition or ligands of the peripheral benzodiazepine receptor. However, release was greatly reduced by the presence of 5% (w/v) dextran (40 kDa), which caused a decrease in the light scattering (A520) of mitochondrial suspensions. Dextran also inhibited both mitochondrial oxidation of exogenous ferrocytochrome c in the presence of rotenone and antimycin, and respiratory-chain-driven reduction of exogenous ferricytochrome c. Hypo-osmotic medium or digitonin treatment of mitochondria caused a large additional release of both cytochrome c and AK that was not blocked by dextran. Polyaspartate, which stabilizes the low conductance state of the voltage-dependent anion channel (VDAC), increased cytochrome c release. VDAC and BAX are both found at the contact sites between the inner and outer membranes and dextran is known to stabilize these contact sites in isolated mitochondria. Thus our data suggest that regulation of a specific permeability pathway for cytochrome c may be mediated by changes in protein-protein interactions within contact sites. The adenine nucleotide translocase is known to bind to VDAC and thus provides an additional link between the specific cytochrome c release pathway and the permeability transition.

scholarly journals ‘Pore’ formation is not required for the hydroperoxide-induced Ca2+ release from rat liver mitochondria

1992 ◽  
Vol 285 (1) ◽  
pp. 65-69 ◽  
Author(s):  
J Schlegel ◽  
M Schweizer ◽  
C Richter
Keyword(s):  
Rat Liver ◽  
Pore Formation ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Specific Permeability ◽  
Specific Pathway

It has recently been suggested by several investigators that the hydroperoxide- and phosphate-induced Ca2+ release from mitochondria occurs through a non-specific ‘pore’ formed in the mitochondrial inner membrane. The aim of the present study was to investigate whether ‘pore’ formation actually is required for Ca2+ release. We find that the t-butyl hydroperoxide (tbh)-induced release is not accompanied by stimulation of sucrose entry into, K+ release from, and swelling of mitochondria provided re-uptake of the released Ca2+ (‘Ca2+ cycling’) is prevented. We conclude that (i) the tbh-induced Ca2+ release from rat liver mitochondria does not require ‘pore’ formation in the mitochondrial inner membrane, (ii) this release occurs via a specific pathway from intact mitochondria, and (iii) a non-specific permeability transition (‘pore’ formation) is likely to be secondary to Ca2+ cycling by mitochondria.

Sign in / Sign up

Export Citation Format

Share Document