1,721,210 research outputs found
Mitochondrial Supercomplexes and ROS Regulation Implications for Ageing
No full textThe simplistic concept that mitochondria are merely the power factories of the cell by way of performing ATP synthesis through oxidative phosphorylation (OXPHOS), and as such that they are discrete semi-autonomous organelles, has given way to the concept of a dynamic network that fuses and divides and is strictly linked to the rest of the cell structures, thereby directing a variety of functions central to cellular life, death and differentiation.1 It is therefore not surprising that mitochondrial dysfunction has emerged as a key factor in a myriad of diseases, including common degenerative and metabolic disorders.2 Moreover, mitochondrial dysfunction is certainly related to the ageing process,3 although the mechanism is still strongly debated.
A major common determinant of the involvement of mitochondria in the aetiology and pathogenesis of so many diseases has been considered their key role in the generation of reactive oxygen species (ROS); although ROS are generated by several other cellular systems, mitochondrial ROS arising from the respiratory chain appear to be strategic for the development of pathological states. Nevertheless, contrary to previous understanding that ROS are deleterious by-products whose production should be avoided, it is now clear that ROS are physiological messengers acting through redox modifications in signalling proteins. For this reason it is believed that ageing may be, at least in part, the result of alterations of signalling pathways such as those involved in mitochondrial biogenesis and apoptosis, induced by an increasing ROS production.4,5
Among the factors controlling ROS generation by mitochondria, it is becoming increasingly clear that a major role is played by the supramolecular structure of mitochondrial respiratory complexes.
The FMN- and CoQ-binding sites of NADH-Coenzyme Q reductase (Complex I) and the Qo site (at the outer or positive side) of ubiquinol-cytochrome c reductase (Complex III) are often invoked as the most important mitochondrial superoxide producers. In the classic model of the electron transfer chain,6 complexes I and III are randomly distributed in the inner mitochondrial membrane (IMM) together with the two other major multi-subunit complexes, designated as succinate-CoQ reductase (Complex II) and cytochrome c oxidase (Complex IV). The enzyme complexes are functionally connected by two redox-active molecules, that is, a lipophilic quinone (Coenzyme Q or ubiquinone, CoQ) embedded in the membrane lipid bilayer, and a hydrophilic heme protein (cytochrome c) localized on the external surface of the IMM.
Contrary to the view of a random organization of the respiratory chain complexes, prevailing in the last decades of the past century,6 evidence has now accumulated that a large proportion of the respiratory complexes in a variety of organisms is arranged in supramolecular assemblies called supercomplexes or respirasomes.7–10
The natural assembly of the respiratory Complexes I, III and IV into supramolecular stoichiometric entities, such as I1III2IV0–4 can have deep functional implications on the properties of the respiratory chain, possibly being enzymatic channelling the most striking consequence of supercomplex association.10–12
There is increasing evidence that supercomplexes are not static assemblies of the individual complexes, but are present in a dynamic state, described by the plasticity model.13
A newly discovered consequence of disruption of supercomplex association is an increase of ROS production.14
In this chapter, we would like to provide experimental evidence that the dynamic nature of supercomplexes is at the basis of a control mechanism of the ROS concentration in the cell. An alteration of this finely tuned mechanism would induce a catastrophic loss of control of ROS generation, culminating in the establishment of a vicious circle of mitochondrial damage and ROS generation that is at the basis of pathological changes. In particular we will provide evidence pertaining to the role that such a vicious circle may have in the ageing process
Isolation and subfractionation of mitochondria from animal cells and tissue culture lines.
No full textBioenergetics theory and components: Quinones
No full textThe reversible oxidation of dihydroxy arenes to the respective quinones is a two-electron process with the intermediate formation of the radical form of semiquinones. The redox systems quinone/diphenol (or quinol) are widely present in nature; they participate in electron transfer chains of eukaryotic cells and bacteria, and are involved in the antioxidant defenses of the cell, as well. This article summarizes the chemical and functional characteristics of some biological naphtho- and benzo-quinones such as vitamin K and Coenzyme Q
Impaired Mitochondrial Bioenergetics under Pathological Conditions
Full text linkMitochondria are the powerhouses of cells; however, mitochondrial dysfunction causes energy depletion and cell death in various diseases [...
Determination of the critical micelle concentration of short-chain ubiquinones in model systems
No full textWe have investigated the critical micelle concentrations of short-chain ubiquinone and ubiquinol homologs in water, aqueous buffers and ethanol-water mixtures. The physical state of ubiquinones becomes nonmonomeric at definite concentration that can be identified because the aggregation is accompanied by a red shift of λmax and a decrease of the extinction coefficient. Systematic studies following the transition dipole moment against quinone concentration have established that the critical micelle concentration is a function of isoprenoid chain length and state of oxidation of the quinones and of the dielectric constant and ionic strength of the medium. The thermodynamics of micelle formation point out that the quinone ring has a strong tendency to be located in a hydrophobic environmen
Understanding differential aspects of microdiffusion (channeling) in the Coenzyme Q and Cytochrome c regions of the mitochondrial respiratory system
Full text linkOver the past decades, models of the organization of mitochondrial respiratory system have been controversial. The goal of this perspective is to assess this “conflict of models” by focusing on specific kinetic evidence in the two distinct segments of Coenzyme Q- and Cytochrome c-mediated electron transfer. Respiratory supercomplexes provide kinetic advantage by allowing a restricted diffusion of Coenzyme Q and Cytochrome c, and short-range interaction with their partner enzymes. In particular, electron transfer from NADH is compartmentalized by channeling of Coenzyme Q within supercomplexes, whereas succinate oxidation proceeds separately using the free Coenzyme Q pool. Previous evidence favoring Coenzyme Q random diffusion in the NADH-dependent electron transfer is due to downstream flux interference and misinterpretation of results. Indeed, electron transfer by complexes III and IV via Cytochrome c is less strictly dependent on substrate channeling in mammalian mitochondria. We briefly describe these differences and their physiological implications
Effects of ketamine anesthesia on rat-brain membranes: fluidity changes and kinetics of acetylcholinesterase.
No full text
Isolation and subfractionation of mitochondria from animal cells and tissue culture lines.
No full textOxidative stress in the denervated muscle.
No full textFree Radic Res. 2010 May;44(5):563-76.
Oxidative stress in the denervated muscle.
Abruzzo PM, di Tullio S, Marchionni C, Belia S, Fanó G, Zampieri S, Carraro U, Kern H, Sgarbi G, Lenaz G, Marini M.
Source
Department of Histology, Embryology, and Applied Biology, University of Bologna, Italy.
Abstract
Following experimental hind limb denervation in rats, this study demonstrates that oxidative stress occurs and advances an hypothesis about its origin. In fact: (i) ROS are formed; (ii) membrane lipids are oxidized; (iii) oxidized ion channels and pumps may lead to increased [Ca(2+)](i); all the above mentioned events increase with denervation time. In the denervated muscle, (iv) mRNA abundance of cytoprotective and anti-oxidant proteins (Hsp70, Hsp27, Sod1, Catalase, Gpx1, Gpx4, Gstm1), as well as (v) SOD1 enzymatic activity and HSP70i protein increase; (vi) an unbalance in mitochondrial OXPHOS enzymes occurs, presumably leading to excess mitochondrial ROS production; (vii) increased cPLA2alpha expression (mRNA) and activation (increased [Ca(2+)](i)) may lead to increased hydroperoxides release. Since anti-oxidant defences appear inadequate to counterbalance increased ROS production with increased denervation time, an anti-oxidant therapeutic strategy seems to be advisable in the many medical conditions where the nerve-muscle connection is impaired.
PMID:
20298122
[PubMed - indexed for MEDLINE
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