1,720,983 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
Where Do We Come From? What Are We? Where Are We Going? - A portrait of the SIB Education Community
No full textDeterminazione dell'ubichinone, dei citocromi e di attività enzimatiche della catena respiratoria in mitocondri cerebrali
No full textThe possible free radical scavenging activity of coenzyme Q detected by a chemiluminescent assay
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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