Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electron reductants

1996 ◽  
Vol 29 (2) ◽  
pp. 169-202 ◽  
Author(s):  
Vladimir P. Skulachev
Keyword(s):  
Resting State ◽  
Mitochondrial Membrane ◽  
High Rate ◽  
Oxygen Species ◽  
Inner Mitochondrial Membrane ◽  
Enzymatic Formation ◽  
Male Sex ◽  
Low Levels ◽  
Cellular Components

AbstractTo proceed at a high rate, phosphorylating respiration requires ADP to be available. In the resting state, when the energy consumption is low, the ADP concentration decreases so that phosphorylating respiration ceases. This may result in an increase in the intracellular concentrations of O2as well as of one-electron O2reductants such asThese two events should dramatically enhance non-enzymatic formation of reactive oxygen species, i.e. of, and OHׁ, and, hence, the probability of oxidative damage to cellular components. In this paper, a concept is put forward proposing that non-phosphorylating (uncoupled or non-coupled) respiration takes part in maintenance of low levels of both O2and the O2reductants when phosphorylating respiration fails to do this job due to lack of ADP.In particular, it is proposed that some increase in the H+leak of mitochondrial membrane in State 4 lowers, stimulates O2consumption and decreases the level ofwhich otherwise accumulates and serves as one-electron O2reductant. In this connection, the role of natural uncouplers (thyroid hormones), recouplers (male sex hormones and progesterone), non-specific pore in the inner mitochondrial membrane, and apoptosis, as well as of non-coupled electron transfer chains in plants and bacteria will be considered.

Mitochondrial Ca2+ Buffering Regulates Synaptic Transmission Between Retinal Amacrine Cells

2002 ◽  
Vol 87 (3) ◽  
pp. 1426-1439 ◽  
Author(s):  
Kathryn Medler ◽  
Evanna L. Gleason
Keyword(s):  
Synaptic Transmission ◽  
Mitochondrial Membrane ◽  
Amacrine Cell ◽  
Critical Role ◽  
Amacrine Cells ◽  
Normal Function ◽  
Inner Mitochondrial Membrane ◽  
Physiological Properties ◽  
Low Levels

The diverse functions of retinal amacrine cells are reliant on the physiological properties of their synapses. Here we examine the role of mitochondria as Ca2+ buffering organelles in synaptic transmission between GABAergic amacrine cells. We used the protonophore p-trifluoromethoxy-phenylhydrazone (FCCP) to dissipate the membrane potential across the inner mitochondrial membrane that normally sustains the activity of the mitochondrial Ca2+ uniporter. Measurements of cytosolic Ca2+ levels reveal that prolonged depolarization-induced Ca2+ elevations measured at the cell body are altered by inhibition of mitochondrial Ca2+ uptake. Furthermore, an analysis of the ratio of Ca2+ efflux on the plasma membrane Na-Ca exchanger to influx through Ca2+ channels during voltage steps indicates that mitochondria can also buffer Ca2+ loads induced by relatively brief stimuli. Importantly, we also demonstrate that mitochondrial Ca2+ uptake operates at rest to help maintain low cytosolic Ca2+ levels. This aspect of mitochondrial Ca2+ buffering suggests that in amacrine cells, the normal function of Ca2+-dependent mechanisms would be contingent upon ongoing mitochondrial Ca2+ uptake. To test the role of mitochondrial Ca2+ buffering at amacrine cell synapses, we record from amacrine cells receiving GABAergic synaptic input. The Ca2+ elevations produced by inhibition of mitochondrial Ca2+uptake are localized and sufficient in magnitude to stimulate exocytosis, indicating that mitochondria help to maintain low levels of exocytosis at rest. However, we found that inhibition of mitochondrial Ca2+ uptake during evoked synaptic transmission results in a reduction in the charge transferred at the synapse. Recordings from isolated amacrine cells reveal that this is most likely due to the increase in the inactivation of presynaptic Ca2+ channels observed in the absence of mitochondrial Ca2+ buffering. These results demonstrate that mitochondrial Ca2+ buffering plays a critical role in the function of amacrine cell synapses.

scholarly journals Monoamine Oxidases as Potential Contributors to Oxidative Stress in Diabetes: Time for a Study in Patients Undergoing Heart Surgery

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Oana M. Duicu ◽  
Rodica Lighezan ◽  
Adrian Sturza ◽  
Raluca A. Ceausu ◽  
Claudia Borza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Membrane ◽  
Ventricular Hypertrophy ◽  
Heart Surgery ◽  
Experimental Studies ◽  
Oxygen Species ◽  
Inner Mitochondrial Membrane ◽  
Monoamine Oxidases ◽  
The Past

Oxidative stress is a pathomechanism causally linked to the progression of chronic cardiovascular diseases and diabetes. Mitochondria have emerged as the most relevant source of reactive oxygen species, the major culprit being classically considered the respiratory chain at the inner mitochondrial membrane. In the past decade, several experimental studies unequivocally demonstrated the contribution of monoamine oxidases (MAOs) at the outer mitochondrial membrane to the maladaptative ventricular hypertrophy and endothelial dysfunction. This paper addresses the contribution of mitochondrial dysfunction to the pathogenesis of heart failure and diabetes together with the mounting evidence for an emerging role of MAO inhibition as putative cardioprotective strategy in both conditions.

Trypanosoma cruzi: death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone

Parasitology ◽  
2018 ◽  
Vol 145 (9) ◽  
pp. 1251-1259 ◽  
Author(s):  
Patricia Andrea Garavaglia ◽  
María Fernanda Rubio ◽  
Marc Laverrière ◽  
Laura Mónica Tasso ◽  
Laura Edith Fichera ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Trypanosoma Cruzi ◽  
Mitochondrial Membrane ◽  
Major Influence ◽  
Ros Production ◽  
Oxygen Species ◽  
Aetiological Agent ◽  
Toxicity Evaluation

AbstractSeveral ortho-naphthoquinones (o-NQs) have trypanocidal activity against Trypanosoma cruzi, the aetiological agent of Chagas disease. Previously, we demonstrated that the aldo-keto reductase from this parasite (TcAKR) reduces o-NQs, such as β-lapachone (β-Lap) and 9,10-phenanthrenequinone (9,10-PQ), with concomitant reactive oxygen species (ROS) production. Recent characterization of TcAKR activity and expression in two T. cruzi strains, CL Brener and Nicaragua, showed that TcAKR expression is 2.2-fold higher in CL Brener than in Nicaragua. Here, we studied the trypanocidal effect and induction of several death phenotypes by β-Lap and 9,10-PQ in epimastigotes of these two strains. The CL Brener strain was more resistant to both o-NQs than Nicaragua, indicating that greater TcAKR activity is unlikely to be a major influence on o-NQ toxicity. Evaluation of changes in ROS production, mitochondrial membrane potential, phosphatidylserine exposure and monodansylcadaverine labelling evidenced that β-Lap and 9,10-PQ induce different death phenotypes depending on the combination of drug and T. cruzi strain analysed. To study whether TcAKR participates in o-NQ activation in intact parasites, β-Lap and 9,10-PQ trypanocidal effect was next evaluated in TcAKR-overexpressing parasites. Only β-Lap was more effective and induced greater ROS production in TcAKR-overexpressing epimastigotes than in controls, suggesting that TcAKR may participate in β-Lap activation.

scholarly journals Expression of a Mitochondrial Peroxiredoxin Prevents Programmed Cell Death in Leishmania donovani

2006 ◽  
Vol 5 (5) ◽  
pp. 861-870 ◽  
Author(s):  
Simone Harder ◽  
Meike Bente ◽  
Kerstin Isermann ◽  
Iris Bruchhaus
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Mitochondrial Membrane ◽  
Leishmania Donovani ◽  
Physiological Role ◽  
Logarithmic Phase ◽  
Insect Vector ◽  
Oxygen Species ◽  
Late Logarithmic Phase

ABSTRACT Leishmania promastigote cells transmitted by the insect vector get phagocytosed by macrophages and convert into the amastigote form. During development and transformation, the parasites are exposed to various concentrations of reactive oxygen species, which can induce programmed cell death (PCD). We show that a mitochondrial peroxiredoxin (LdmPrx) protects Leishmania donovani from PCD. Whereas this peroxiredoxin is restricted to the kinetoplast area in promastigotes, it covers the entire mitochondrion in amastigotes, accompanied by dramatically increased expression. A similar change in the expression pattern was observed during the growth of Leishmania from the early to the late logarithmic phase. Recombinant LdmPrx shows typical peroxiredoxin-like enzyme activity. It is able to detoxify organic and inorganic peroxides and prevents DNA from hydroxyl radical-induced damage. Most notably, Leishmania parasites overexpressing this peroxiredoxin are protected from hydrogen peroxide-induced PCD. This protection is also seen in promastigotes grown to the late logarithmic phase, also characterized by high expression of this peroxiredoxin. Apparently, the physiological role of this peroxiredoxin is stabilization of the mitochondrial membrane potential and, as a consequence, inhibition of PCD through removal of peroxides.

Cytoprotective Role of Ca2+- Activated K+ Channels in the Cardiac Inner Mitochondrial Membrane

Science ◽  
2002 ◽  
Vol 298 (5595) ◽  
pp. 1029-1033 ◽  
Author(s):  
W. Xu ◽  
Y. Liu ◽  
S. Wang ◽  
T. McDonald ◽  
J. E. Van Eyk ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Inner Mitochondrial Membrane ◽  
K Channels

scholarly journals Inhibition of the Anti-Apoptotic Bcl-2 Family by BH3 Mimetics Sensitize the Mitochondrial Permeability Transition Pore Through Bax and Bak

2021 ◽  
Vol 9 ◽  
Author(s):  
Pooja Patel ◽  
Arielys Mendoza ◽  
Dexter J. Robichaux ◽  
Meng C. Wang ◽  
Xander H. T. Wehrens ◽  
...  
Keyword(s):  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Family Member ◽  
Mitochondrial Membrane ◽  
Mitochondrial Permeability Transition ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Inner Mitochondrial Membrane ◽  
Retention Capacity

Mitochondrial permeability transition pore (MPTP)-dependent necrosis contributes to numerous pathologies in the heart, brain, and skeletal muscle. The MPTP is a non-selective pore in the inner mitochondrial membrane that is triggered by high levels of matrix Ca2+, and sustained opening leads to mitochondrial dysfunction. Although the MPTP is defined by an increase in inner mitochondrial membrane permeability, the expression of pro-apoptotic Bcl-2 family members, Bax and Bak localization to the outer mitochondrial membrane is required for MPTP-dependent mitochondrial dysfunction and subsequent necrotic cell death. Contrary to the role of Bax and Bak in apoptosis, which is dependent on their oligomerization, MPTP-dependent necrosis does not require oligomerization as monomeric/inactive forms of Bax and Bak can facilitate mitochondrial dysfunction. However, the relationship between Bax and Bak activation/oligomerization and MPTP sensitization remains to be explored. Here, we use a combination of in vitro and ex vivo approaches to determine the role of the anti-apoptotic Bcl-2 family members, which regulate Bax/Bak activity, in necrotic cell death and MPTP sensitivity. To study the role of each predominantly expressed anti-apoptotic Bcl-2 family member (i.e., Mcl-1, Bcl-2, and Bcl-xL) in MPTP regulation, we utilize various BH3 mimetics that specifically bind to and inhibit each. We determined that the inhibition of each anti-apoptotic Bcl-2 family member lowers mitochondrial calcium retention capacity and sensitizes MPTP opening. Furthermore, the inhibition of each Bcl-2 family member exacerbates both apoptotic and necrotic cell death in vitro in a Bax/Bak-dependent manner. Our findings suggests that mitochondrial Ca2+ retention capacity and MPTP sensitivity is influenced by Bax/Bak activation/oligomerization on the outer mitochondrial membrane, providing further evidence of the crosstalk between the apoptotic and necrotic cell death pathways.

scholarly journals Pyrite Biooxidation by Acidophilic Archaea AcidiplasmaSp. MBA-1 Under Varied Conditions

2022 ◽  
Author(s):  
Aleksandr Bulaev
Keyword(s):  
Potential Role ◽  
Sulfide Mineral ◽  
High Rate ◽  
Mineral Nutrient ◽  
Acidophilic Microorganisms ◽  
Moderately Thermophilic ◽  
Operational Temperature ◽  
Low Levels ◽  
Acidophilic Archaea

The goal of this research was to study pyrite (FeS2 ) bioleaching by a strain of the genus Acidiplasma under different conditions (temperature, pH) to evaluate the potential role of Acidiplasma representatives in biooxidation of this sulfide mineral. To compare the role of Acidiplasma archaea in pyrite biooxidation with other acidophilic microorganisms, the experiments were also performed with representatives of othergroups of microorganisms predominant in biohydrometallurgical processes.Pure and mixed cultures of moderately thermophilic acidophilic microorganisms, including strains Acidithiobacillus caldus MBC-1, Sulfobacillusthermosulfidooxidans VKMV 1269T and Acidiplasmasp. MBA-1, were used. The experiments were carried out in flasks with 100 mL of mineral nutrient medium supplemented with 0.02% yeast extract and 1 g of pyrite on a rotary shaker for 20 days. Bioleaching was performed at 45, 55, and 60∘С. The results demonstrated that the representatives of the genus Acidiplasmaprovided a comparatively higher rate of pyrite bioleaching at high temperatures (55 and 60∘C) and low pH of the medium (1.0). Thus, according to the results, strains of thegenus Acidiplasma may provide a high rate of pyrite bioleaching at low levels ofpH. Therefore, the results suggest that archaea of the genus Acidiplasma may be promising microorganisms to improve bioleaching processes with an increase in the operational temperature, which is usually maintained at 40–45∘C in industrial-scale reactors. Keywords: biomining, bioleaching, acidophilic microorganisms, sulfide minerals, pyrite

scholarly journals Circulating levels of mitochondrial uncoupling protein 2, but not prohibitin, are lower in humans with type 2 diabetes and correlate with brachial artery flow-mediated dilation

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Mamatha Kakarla ◽  
Venkata K. Puppala ◽  
Sudhi Tyagi ◽  
Amberly Anger ◽  
Kathryn Repp ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Flow Mediated Dilation ◽  
Vascular Health ◽  
Oxygen Species ◽  
Inner Mitochondrial Membrane ◽  
Artery Flow ◽  
Circulating Levels

Abstract Background Excessive reactive oxygen species from endothelial mitochondria in type 2 diabetes individuals (T2DM) may occur through multiple related mechanisms, including production of mitochondrial reactive oxygen species (mtROS), inner mitochondrial membrane (Δψm) hyperpolarization, changes in mitochondrial mass and membrane composition, and fission of the mitochondrial networks. Inner mitochondrial membrane proteins uncoupling protein-2 (UCP2) and prohibitin (PHB) can favorably impact mtROS and mitochondrial membrane potential (Δψm). Circulating levels of UCP2 and PHB could potentially serve as biomarker surrogates for vascular health in patients with and without T2DM. Methods Plasma samples and data from a total of 107 individuals with (N = 52) and without T2DM (N = 55) were included in this study. Brachial artery flow mediated dilation (FMD) was measured by ultrasound. ELISA was performed to measure serum concentrations of PHB1 and UCP2. Mitochondrial membrane potential was measured from isolated leukocytes using JC-1 dye. Results Serum UCP2 levels were significantly lower in T2DM subjects compared to control subjects (3.01 ± 0.34 vs. 4.11 ± 0.41 ng/mL, P = 0.04). There were no significant differences in levels of serum PHB. UCP2 levels significantly and positively correlated with FMDmm (r = 0.30, P = 0.03) in T2DM subjects only and remained significant after multivariable adjustment. Within T2DM subjects, serum PHB levels were significantly and negatively correlated with UCP2 levels (ρ = − 0.35, P = 0.03). Conclusion Circulating UCP2 levels are lower in T2DM patients and correlate with endothelium-dependent vasodilation in conduit vessels. UCP2 could be biomarker surrogate for overall vascular health in patients with T2DM and merits additional investigation.

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