1,721,033 research outputs found
The inhibitor protein (IF1) of the F1F0-ATPase modulates human osteosarcoma cell bioenergetics
No full textThe bioenergetics of IF1 transiently silenced cancer cells has been extensively investigated, but the role of IF1 (the natural inhibitor protein of F1F0-ATPase) in cancer cell metabolism is still uncertain. To shed light on this issue, we established a method to prepare stably IF1-silenced human osteosarcoma clones and explored the bioenergetics of IF1 null cancer cells. We showed that IF1-silenced cells proliferate normally, consume glucose, and release lactate as controls do, and contain a normal steady-state ATP level. However, IF1-silenced cells displayed an enhanced steady-state mitochondrial membrane potential and consistently showed a reduced ADP-stimulated respiration rate. In the parental cells (i.e. control cells containing IF1) the inhibitor protein was found to be associated with the dimeric form of the ATP synthase complex, therefore we propose that the interaction of IF1 with the complex either directly, by increasing the catalytic activity of the enzyme, or indirectly, by improving the structure of mitochondrial cristae, can increase the oxidative phosphorylation rate in osteosarcoma cells grown under normoxic conditions
The F1Fo-ATPase inhibitor protein IF1 in pathophysiology
Full text linkThe endogenous inhibitor of ATP synthase is a protein of about 10 kDa, known as IF1 which binds to the catalytic domain of the enzyme during ATP hydrolysis. The main role of IF1 consists of limiting ATP dissipation under condition of severe oxygen deprivation or in the presence of dysfunctions of mitochondrial respiratory complexes, causing a collapse in mitochondrial membrane potential and therefore ATP hydrolysis. New roles of IF1 are emerging in the fields of cancer and neurodegeneration. Its high expression levels in tumor tissues have been associated with different roles favouring tumor formation, progression and evasion. Since discordant mechanisms of action have been proposed for IF1 in tumors, it is of the utmost importance to clarify them in the prospective of defining novel approaches for cancer therapy. Other IF1 functions, including its involvement in mitophagy, may be protective for neurodegenerative and aging-related diseases. In the present review we aim to clarify and discuss the emerging mechanisms in which IF1 is involved, providing a critical view of the discordant findings in the literature
Variants in Human ATP Synthase Mitochondrial Genes: Biochemical Dysfunctions, Associated Diseases, and Therapies
Full text link: Mitochondrial ATP synthase (Complex V) catalyzes the last step of oxidative phosphorylation and provides most of the energy (ATP) required by human cells. The mitochondrial genes MT-ATP6 and MT-ATP8 encode two subunits of the multi-subunit Complex V. Since the discovery of the first MT-ATP6 variant in the year 1990 as the cause of Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP) syndrome, a large and continuously increasing number of inborn variants in the MT-ATP6 and MT-ATP8 genes have been identified as pathogenic. Variants in these genes correlate with various clinical phenotypes, which include several neurodegenerative and multisystemic disorders. In the present review, we report the pathogenic variants in mitochondrial ATP synthase genes and highlight the molecular mechanisms underlying ATP synthase deficiency that promote biochemical dysfunctions. We discuss the possible structural changes induced by the most common variants found in patients by considering the recent cryo-electron microscopy structure of human ATP synthase. Finally, we provide the state-of-the-art of all therapeutic proposals reported in the literature, including drug interventions targeting mitochondrial dysfunctions, allotopic gene expression- and nuclease-based strategies, and discuss their potential translation into clinical trials
Increased state 4 mitochondrial respiration and swelling in early post-ischemic reperfusion of rat heart
No full textAbstractIsolated rat hearts were exposed to 30 min ischemia or to 30 min ischemia followed by 2, 5 or 40 min reperfusion and mitochondria were isolated at these different time points. ADP-stimulated, succinate-dependent respiration rate (state 3) was not significantly changed at the different time points examined. In contrast, state 4 (non-ADP-stimulated) respiration rate was significantly increased after 30 min ischemia, and it increased further during the first post-ischemic reperfusion period. Mitochondrial swelling, as evaluated under conditions of the major controlled ion channels (i.e. permeability transition pore and ATP-dependent mitochondrial K+ channel) closed, significantly increased in parallel. It is suggested that the inner mitochondrial membrane permeability is increased under exposure of the heart to ischemia and early reperfusion, and that the phenomenon is reversible upon subsequent long periods of reperfusion
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
The ATP synthase deficiency in human diseases
Full text linkHuman diseases range from gene-associated to gene-non-associated disorders, including age-related diseases, neurodegenerative, neuromuscular, cardiovascular, diabetic diseases, neurocognitive disorders and cancer. Mitochondria participate to the cascades of pathogenic events leading to the onset and progression of these diseases independently of their association to mutations of genes encoding mitochondrial protein. Under physiological conditions, the mitochondrial ATP synthase provides the most energy of the cell via the oxidative phosphorylation. Alterations of oxidative phosphorylation mainly affect the tissues characterized by a high-energy metabolism, such as nervous, cardiac and skeletal muscle tissues. In this review, we focus on human diseases caused by altered expressions of ATP synthase genes of both mitochondrial and nuclear origin. Moreover, we describe the contribution of ATP synthase to the pathophysiological mechanisms of other human diseases such as cardiovascular, neurodegenerative diseases or neurocognitive disorders
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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