scholarly journals Biguanides Inhibit Complex I, II and IV of Rat Liver Mitochondria and Modify Their Functional Properties

2014 ◽  
pp. 1-11 ◽  
Author(s):  
Z. DRAHOTA ◽  
E. PALENICKOVA ◽  
R. ENDLICHER ◽  
M. MILEROVA ◽  
J. BREJCHOVA ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Rat Liver ◽  
Enzyme Activities ◽  
Complex I ◽  
Mitochondrial Membrane ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria

In this study, we focused on an analysis of biguanides effects on mitochondrial enzyme activities, mitochondrial membrane potential and membrane permeability transition pore function. We used phenformin, which is more efficient than metformin, and evaluated its effect on rat liver mitochondria and isolated hepatocytes. In contrast to previously published data, we found that phenformin, after a 5 min pre-incubation, dose-dependently inhibits not only mitochondrial complex I but also complex II and IV activity in isolated mitochondria. The enzymes complexes inhibition is paralleled by the decreased respiratory control index and mitochondrial membrane potential. Direct measurements of mitochondrial swelling revealed that phenformin increases the resistance of the permeability transition pore to Ca2+ ions. Our data might be in agreement with the hypothesis of Schäfer (1976) that binding of biguanides to membrane phospholipids alters membrane properties in a non-specific manner and, subsequently, different enzyme activities are modified via lipid phase. However, our measurements of anisotropy of fluorescence of hydrophobic membrane probe diphenylhexatriene have not shown a measurable effect of membrane fluidity with the 1 mM concentration of phenformin that strongly inhibited complex I activity. Our data therefore suggest that biguanides could be considered as agents with high efficacy but low specifity.

scholarly journals T-2307 Causes Collapse of Mitochondrial Membrane Potential in Yeast

2012 ◽  
Vol 56 (11) ◽  
pp. 5892-5897 ◽  
Author(s):  
Tatsuya Shibata ◽  
Toshinari Takahashi ◽  
Eio Yamada ◽  
Akiko Kimura ◽  
Hiroshi Nishikawa ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Rat Liver ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Liver Mitochondria ◽  
Yeast Cells ◽  
Rat Liver Mitochondria ◽  
Content Type ◽  
Glycerol Medium

ABSTRACTT-2307, an arylamidine compound, has been previously reported to have broad-spectrumin vitroandin vivoantifungal activities against clinically significant pathogens, includingCandidaspecies,Cryptococcus neoformans, andAspergillusspecies, and is now undergoing clinical trials. Here we investigated the mechanism of action of T-2307 using yeast cells and mitochondria isolated from yeast and rat liver. Nonfermentative growth ofCandida albicansandSaccharomyces cerevisiaein glycerol medium, in which yeasts relied on mitochondrial respiratory function, was inhibited at 0.001 to 0.002 μg/ml (0.002 to 0.004 μM) of T-2307. However, fermentative growth in dextrose medium was not inhibited by T-2307. Microscopic examination using Mitotracker fluorescent dye, a cell-permeant mitochondrion-specific probe, demonstrated that T-2307 impaired the mitochondrial function ofC. albicansandS. cerevisiaeat concentrations near the MIC in glycerol medium. T-2307 collapsed the mitochondrial membrane potential in mitochondria isolated fromS. cerevisiaeat 20 μM. On the other hand, in isolated rat liver mitochondria, T-2307 did not have any effect on the mitochondrial membrane potential at 10 mM. Moreover, T-2307 had little inhibitory and stimulatory effect on mitochondrial respiration in rat liver mitochondria. In conclusion, T-2307 selectively disrupted yeast mitochondrial function, and it was also demonstrated that the fungal mitochondrion is an attractive antifungal target.

scholarly journals Age-Dependent Changes in the Function of Mitochondrial Membrane Permeability Transition Pore in Rat Liver Mitochondria

2021 ◽  
pp. 905-911
Author(s):  
R. Endlicher ◽  
Z. Drahota ◽  
O. Kučera ◽  
Z. Červinková
Keyword(s):  
Rat Liver ◽  
Mitochondrial Membrane ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Cell Aging ◽  
Rat Liver Mitochondria ◽  
Age Related ◽  
Old Rats

Mitochondria play an important role in the cell aging process. Changes in calcium homeostasis and/or increased reactive oxygen species (ROS) production lead to the opening of mitochondrial permeability transition pore (MPTP), depolarization of the inner mitochondrial membrane, and decrease of ATP production. Our work aimed to monitor age-related changes in the Ca2+ ion effect on MPTP and the ability of isolated rat liver mitochondria to accumulate calcium. The mitochondrial calcium retention capacity (CRC) was found to be significantly affected by the age of rats. Measurement of CRC values of the rat liver mitochondria showed two periods when 3 to17-week old rats were tested. 3-week and 17-week old rats showed lower CRC values than 7-week old animals. Similar changes were observed while testing calcium-induced swelling of rat liver mitochondria. These findings indicate that the mitochondrial energy production system is more resistant to calcium-induced MPTP opening accompanied by the damaging effect of ROS in adult rats than in young and aged animals.

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.

scholarly journals Mitochondria Permeabilization by a Novel Polycation Peptide BTM-P1

2005 ◽  
Vol 280 (16) ◽  
pp. 15579-15586 ◽  
Author(s):  
Victor V. Lemeshko ◽  
Mauricio Arias ◽  
Sergio Orduz
Keyword(s):  
Membrane Potential ◽  
Cyclosporin A ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Peptide Sequence ◽  
Rat Liver Mitochondria ◽  
Tryptophan Residue ◽  
Inner Membrane

Bacillus thuringiensissubsp.medellinis known to produce the Cry11Bb protein of 94 kDa, which is toxic for mosquito larvae due to permeabilization of the plasma membrane of midgut epithelial cells. Earlier we found that a 2.8-kDa novel peptide BTM-P1, which was artificially synthesized taking into account the primary structure of Cry11Bb endotoxin, is active against several species of bacteria. In this work we show that BTM-P1 induces cyclosporin A-insensitive swelling of rat liver mitochondria in various salt solutions but not in the sucrose medium. Inorganic phosphate and Ca2+significantly increased this effect of the peptide. The uncoupling action of BTM-P1 on oxidative phosphorylation was stronger in the potassium-containing media and correlated with a decrease of the inner membrane potential of mitochondria. In isotonic KNO3, KCl, or NH4NO3media, a complete drop of the inner membrane potential was observed at 1–2 μg/ml of the peptide. The peptide-induced swelling was increased by energization of mitochondria in the potassium-containing media, but it was inhibited in the NaNO3, NH4NO3, and Tris-NO3media. All mitochondrial effects of the peptide were completely prevented by adding a single N-terminal tryptophan residue to the peptide sequence. We suggest a mechanism of membrane permeabilization that includes a transmembrane- and surface potential-dependent insertion of the polycation peptide into the lipid bilayer and its oligomerization leading to formation of ion channels and also to the mitochondrial permeability transition pore opening in a cyclosporin A-insensitive manner.

Accumulation of D-arginine by rat liver mitochondria

1987 ◽  
Vol 65 (12) ◽  
pp. 1057-1063 ◽  
Author(s):  
Rafael Villalobos-Molina ◽  
J. Pablo Pardo ◽  
Alfredo Saavedra-Molina ◽  
Enrique Piña
Keyword(s):  
Membrane Potential ◽  
Rat Liver ◽  
Mitochondrial Respiration ◽  
Mitochondrial Membrane ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Inner Mitochondrial Membrane ◽  
Osmotic Swelling ◽  
Dose Dependent Fashion ◽  
Dose Dependent

The permeability of the inner mitochondrial membrane from rat liver to D-arginine was studied. By using safranin as a probe of the membrane potential, depolarization of energized liver mitochondria occurred in a dose-dependent fashion starting at 3.3 mmol/L of D- or DL-arginine. When ethidium bromide fluorescence was employed, a decrease in the membrane potential due to D- or DL-arginine was observed. A parallel significant change in succinate-induced respiration in rat liver mitochondria was found in response to osmotic swelling in 125 mmol/L of D-arginine salts. L-Arginine, L-glutamine, L-asparagine, L-ornithine, D-ornithine, and L-lysine did not modify the membrane potential at the concentrations tested. D-Arginine was not transformed into citrulline, but 1.0 mmol/L of the D-amino acid inhibited, by 42%, the state 3 of mitochondrial respiration using succinate as substrate. When D-arginine was used in combination with nigericin, a 40% inhibition of mitochondrial respiration in state 3 was recorded with succinate and with glutamate–malate as substrates.

scholarly journals Methylmercury induces the opening of the permeability transition pore in rat liver mitochondria

2002 ◽  
Vol 89 (1-2) ◽  
pp. 159-162 ◽  
Author(s):  
Marcantonio Bragadin ◽  
Daniele Marton ◽  
Sabrina Manente ◽  
Mario Grasso ◽  
Antonio Toninello
Keyword(s):  
Rat Liver ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria

scholarly journals Functional activity of permeability transition pore in energized and deenergized rat liver mitochondria

2020 ◽  
Vol 92 (6) ◽  
pp. 63-76
Author(s):  
O. V. Akopova ◽  
◽  
L. I. Kolchinskaya ◽  
V. I. Nosar Kolchinskaya ◽  
◽  
...  
Keyword(s):  
Rat Liver ◽  
Functional Activity ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria
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