Safari with an Electron Gun: Visualization of Protein and Membrane Interactions in Mitochondria in Natural Environment.

This paper presents new structural data about mitochondria using correlative light and electron microscopy (CLEM) and cryo-electron tomography. These state-of-the-art structural biology methods allow studying biological objects at nanometer scales under natural conditions. Non-invasiveness of these methods makes them comparable to observing animals in their natural environment on a safari.

Directed proton transfer from F to F extends the multifaceted proton functions in ATP synthase.

The role of protons in ATP synthase is typically considered to be energy storage in the form of an electrochemical potential, as well as an operating element proving rotation. However, this review emphasizes that protons also act as activators of conformational changes in F and as direct participants in phosphorylation reaction. The protons transferred through F do not immediately leave to the bulk aqueous phase, but instead provide for the formation of a pH gradient between acidifying F and alkalizing F.

Association of 2-oxoacid dehydrogenase complexes with respirasomes in mitochondria.

In the present study, cryo-electron tomography was used to investigate the localization of 2-oxoacid dehydrogenase complexes (OADCs) in cardiac mitochondria and mitochondrial inner membrane samples. Two classes of ordered OADC inner cores with different symmetries were distinguished and their quaternary structures modeled. One class corresponds to pyruvate dehydrogenase complexes and the other to dehydrogenase complexes of α-ketoglutarate and branched-chain α-ketoacids.

Contribution of the Collective Excitations to the Coupled Proton and Energy Transport along Mitochondrial Cristae Membrane in Oxidative Phosphorylation System.

The results of many experimental and theoretical works indicate that after transport of protons across the mitochondrial inner membrane (MIM) in the oxidative phosphorylation (OXPHOS) system, they are retained on the membrane-water interface in nonequilibrium state with free energy excess due to low proton surface-to-bulk release. This well-established phenomenon suggests that proton trapping on the membrane interface ensures vectorial lateral transport of protons from proton pumps to ATP synthases (proton acceptors). Despite the key role of the proton transport in bioenergetics, the molecular mechanism of proton transfer in the OXPHOS system is not yet completely established.

Mechanism of Energy Storage and Transformation in the Mitochondria at the Water-Membrane Interface.

In this review, we discuss the mechanisms of generation of membrane-bound protons using different energy sources in model and natural systems. Analysis of these mechanisms revealed that all three types of reactions include the same principal stage, which is dissociation of electrically neutral Brønsted acids at the interface during transition from the hydrophobic phase to water with a low dielectric constant. Special attention is paid to the fact that in one of the analyzed model systems, membrane-bound protons provide energy for the reaction of ATP synthesis.

Structural and functional roles of non-bilayer lipid phases of chloroplast thylakoid membranes and mitochondrial inner membranes.

The 'standard' fluid-mosaic membrane model can provide a framework for the operation of the photosynthetic and respiratory electron transport systems, the generation of the proton motive force (pmf) and its utilization for ATP synthesis according to the chemiosmotic theory. However, this model, with the bilayer organization of all lipid molecules, assigns no function to non-bilayer lipids - while in recent years it became clear that the two fundamental energy transducing membranes of the biosphere, chloroplast thylakoid membranes (TMs) and inner mitochondrial membranes (IMMs), contain large amounts of non-bilayer (non-lamellar) lipid phases. In this review, we summarize our understanding on the role of non-lamellar phases in TMs and IMMs: (i) We propose that for these membrane vesicles the dynamic exchange model (DEM) provides a more suitable framework than the 'standard' model; DEM complements the 'standard' model by assuming the co-existence of bilayer and non-bilayer phases and their interactions, which contribute to the structural dynamics of the membrane systems and safe-guard the membranes' high protein:lipid ratios.

Cardiolipin, Non-Bilayer Structures and Mitochondrial Bioenergetics: Relevance to Cardiovascular Disease.

The present review is an attempt to conceptualize a contemporary understanding about the roles that cardiolipin, a mitochondrial specific conical phospholipid, and non-bilayer structures, predominantly found in the inner mitochondrial membrane (IMM), play in mitochondrial bioenergetics. This review outlines the link between changes in mitochondrial cardiolipin concentration and changes in mitochondrial bioenergetics, including changes in the IMM curvature and surface area, cristae density and architecture, efficiency of electron transport chain (ETC), interaction of ETC proteins, oligomerization of respiratory complexes, and mitochondrial ATP production. A relationship between cardiolipin decline in IMM and mitochondrial dysfunction leading to various diseases, including cardiovascular diseases, is thoroughly presented.

Correction: Genotoxic effect of 2,2'-bis(bicyclo[2.2.1] heptane) on bacterial cells.

[This corrects the article DOI: 10.1371/journal.pone.

Ordered Clusters of the Complete Oxidative Phosphorylation System in Cardiac Mitochondria.

The existence of a complete oxidative phosphorylation system (OXPHOS) supercomplex including both electron transport system and ATP synthases has long been assumed based on functional evidence. However, no structural confirmation of the docking between ATP synthase and proton pumps has been obtained. In this study, cryo-electron tomography was used to reveal the supramolecular architecture of the rat heart mitochondria cristae during ATP synthesis.

Genotoxic effect of 2,2'-bis(bicyclo[2.2.1] heptane) on bacterial cells.

The toxic effect of strained hydrocarbon 2,2'-bis (bicyclo[2.2.1]heptane) (BBH) was studied using whole-cell bacterial lux-biosensors based on Escherichia coli cells in which luciferase genes are transcriptionally fused with stress-inducible promoters.

Amino Acids as Regulators of Cell Metabolism.

In this review, we discuss the principles of regulation and synchronization of metabolic processes in mammalian cells using a two-component model of cell metabolism consisting of a controlling signaling system that regulates major enzymatic cascades and executive metabolic system that directly performs biosynthetic reactions. This approach has allowed us to distinguish two transitional metabolic states (from catabolism to anabolism and vice versa) accompanied by major rearrangements in the signaling system. The signaling system of natural amino acids was selected, because amino acids are involved in both signaling and executive metabolic subsystems of general cell metabolism.

NMDA and GABA receptor presence in rat heart mitochondria.

The purpose of this study is to demonstrate the presence of three more receptors in mitochondria. Two N-methyl-d-aspartate receptor (NMDAR) subunits (NR1 and NR2B) are found by protein immunoblot and immunogold labeling in mitochondria fraction isolated from rat heart. These data allow supposing NMDAR presence and functioning in the inner mitochondrial membrane.

Non-bilayer structures in mitochondrial membranes regulate ATP synthase activity.

Cardiolipin (CL) is an anionic phospholipid at the inner mitochondrial membrane (IMM) that facilitates the formation of transient non-bilayer (non-lamellar) structures to maintain mitochondrial integrity. CL modulates mitochondrial functions including ATP synthesis. However, the biophysical mechanisms by which CL generates non-lamellar structures and the extent to which these structures contribute to ATP synthesis remain unknown.

On the regulative role of the glutamate receptor in mitochondria.

The purpose of this work was to study the regulative role of the glutamate receptor found earlier in the brain mitochondria. In the present work a glutamate-dependent signaling system with similar features was detected in mitochondria of the heart. The glutamate-dependent signaling system in the heart mitochondria was shown to be suppressed by γ-aminobutyric acid (GABA).

[Continuous Generation of Hydrogen Peroxide in Water Containing Very Low Concentrations of Unsymmetrical Dimethylhydrazine].

Continuous generation of hydrogen peroxide catalyzed by low concentrations of 1,1-dimethylhydrazine (heptyl)--a rocket fuel component--in air saturated water was shown by the method of enhanced chemiluminescence in the system of luminol-p-iodophenol-peroxidase. The concentration dependence and the influence of heat and light on the formation of hydrogen peroxide in the water under the influence of dimethylhydrazine at concentrations considerably lower than maximum allowable concentrations were studied, and the physical-chemical mechanism of this process was considered. It is supposed that dimethylhydrazine at ultra-low concentrations is associated with air nanobubbles and represents a long-lived complex performing catalysis of hydrogen peroxide formation under the influence of heat and light.

On Local Coupling of Electron Transport and ATP-Synthesis System in Mitochondria. Theory and Experiment.

A brief description of the principal directions for searching and investigating the model of local coupling between respiration and phosphorylation proposed by R. Williams is given in this paper. We found conditions where it was possible to reveal typical functional special features of the mitochondrial phosphorylating system.

Glutamate induces H2O2 synthesis in nonsynaptic brain mitochondria.

Mitochondrial reactive oxygen species regulate many important biological processes. We studied H2O2 formation by nonsynaptic brain mitochondria in response to the addition of low concentrations of glutamate, an excitatory neurotransmitter. We demonstrated that glutamate at concentrations from 10 to 50 μM stimulated the H2O2 generation in mitochondria up to 4-fold, in a dose-dependent manner.

Mechanism underlying the protective effect of glycine in energetic disturbances in brain tissues under hypoxic conditions.

Glycine stabilizes energetics of brain mitochondria under conditions of brain hypoxia in vivo modeled by ligation of the common carotid artery in rats. Hypoxia reduced respiratory control in brain cortex mitochondria from 7.7 ± 0.

Oxygen-dependent auto-oscillations of water luminescence triggered by the 1264 nm radiation.

A 5-min exposure of air-saturated bidistilled water to low-intensity laser infrared radiation at the wavelength of the electronic transition of dissolved oxygen to the singlet state ((3)∑(g)(-)→ (1)Δ(g)) induces, after a long latent period, auto-oscillations of water luminescence in the blue-green region, which last many hours. Laser irradiation causes the accumulation of hydrogen peroxide, which depends on the concentration of dissolved oxygen. The auto-oscillations do not arise if water is irradiated beyond the oxygen absorption band and if the oxygen is removed from water.

Penetrating cation/fatty acid anion pair as a mitochondria-targeted protonophore.

A unique phenomenon of mitochondria-targeted protonophores is described. It consists in a transmembrane H(+)-conducting fatty acid cycling mediated by penetrating cations such as 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) or dodecyltriphenylphosphonium (C(12)TPP). The phenomenon has been modeled by molecular dynamics and directly proved by experiments on bilayer planar phospholipid membrane, liposomes, isolated mitochondria, and yeast cells.

Molecular mechanisms of transformation of SkQ mitotropic quinones and the search for new approaches to creation of selective free radical traps.

Features of the mechanism of action of positively charged benzoquinone derivatives (SkQ), which are the analogs of coenzyme Q (I), plastoquinone (II), and tocopherol (III), are discussed. It is usually considered that the main target of these compounds is mitochondria, where they accumulate due to the positive charge of the molecule. In the present work, it is shown with model systems that the reduced forms of compounds (I-III) under certain conditions can transform into electrically neutral cyclic zwitterions, which theoretically can escape from the matrix of energized mitochondria against the concentration gradient.

An attempt to prevent senescence: a mitochondrial approach.

Antioxidants specifically addressed to mitochondria have been studied to determine if they can decelerate senescence of organisms. For this purpose, a project has been established with participation of several research groups from Russia and some other countries. This paper summarizes the first results of the project.

Diversity of neurodegenerative processes in the model of brain cortex tissue ischemia.

Stroke is known to induce massive cell death in the ischemic brain. Either necrotic or apoptotic types of cell death program were observed in neurons in zone of ischemia. We suggest that spatial heterogeneity of glucose and oxygen distribution plays a crucial role in this phenomenon.