Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Che1/AATF interacts with subunits of the histone acetyltransferase core module of SAGA complexes

WOS: 000417698200025PubMed ID: 29232376General Control Non-derepressible 5 (GCN5) and Alteration/Deficiency in Activation 2 and 3 proteins (ADA2 and ADA3, respectively) are subunits of the Histone AcetylTransferase (HAT) module of SAGA-and ATAC-type co-activators. We previously reported four new interacting partners of human ADA3 identified by screening a human fetal brain cDNA library using yeast two hybrid technology. One of these partners was Apoptosis-Antagonizing Transcription Factor (AATF), also known as Che-1, an RNA polymerase II-binding protein with a number of roles in different cellular processes including regulation of transcription, cell proliferation, cell cycle control, DNA damage responses and apoptosis. Che-1/AATF is a potential therapeutic target for cancer treatments. In this study, we aimed to identify whether besides ADA3, other components of the HAT modules of SAGA and ATAC complexes, human ADA2 and GCN5 also interact with Che-1/AATF. Co-immunoprecipitation and co-localization experiments were used to demonstrate association of AATF both with two ADA2 isoforms, ADA2A and ADA2B and with GCN5 proteins in human cells and yeast two-hybrid assays to delineate domains in the ADA2 and GCN5 proteins required for these interactions. These findings provide new insights into the pathways regulated by ADA-containing protein complexes.Turkish Scientific and Technological Research Assembly [112T429]; Hungarian NRDIO [GINOP-2.3.2-15-2016-00020]This work was supported by the Turkish Scientific and Technological Research Assembly (112T429) (Dr. Sevil Zencir), and Hungarian NRDIO-GINOP-2.3.2-15-2016-00020 (Prof Imre M. Boros). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The sequences of the primers used in the amplification of corresponding genes.

<p>The sequences of the primers used in the amplification of corresponding genes.</p

Co-localizations of ADA2A, ADA2B, GCN5 with AATF protein in HEK293 cells.

<p>Intracellular co-localization of CFP-conjugated ADA2A (A), ADA2B (B), GCN5 (C), empty vector expressing CFP alone (D) and YFP-conjugated AATF proteins (middle column). Yellow color in the merged image (last column) indicates co-localization. Live cell images were captured by confocal microscopy and pseudo-coloured red (CFP) and green (YFP). Insets show single transfections. Upper right corners of nuclei are marked with a curved line. The last column shows merged images. Scale bar is 5 μm.</p

Effect of co-expression of ADA2A, ADA2B, GCN5 with AATF on the expression of an MDM2 promoter-luciferase reporter gene.

<p>U2OS cells were transfected with a reporter plasmid encoding a luciferase gene under the control of the MDM2 promoter or co-transfected with the reporter plasmid and plasmids expressing ADA2A, ADA2B, GCN5 with AATF protein partner as indicated. Luciferase activity was measured 48 h post-transfection. Results represent the average ± SD from three independent assays. Co-expression of AATF with ADA2A, ADA2B or GCN5, significantly reduced the activation imparted by AATF on MDM2 promoter-directed transcription (<i>p</i> <0.01).</p

Toward a Research Agenda on Digital Media and Humanity Well-Being

In the 2020s, an American citizen will spend an average of 6h35 a day on social media, compared to 3h35 for television. As for social networks, which were non-existent less than 20 years ago, about 40\% of US citizens use them at least once a week as source of news and they now have an estimated 60-70% penetration rate worldwide.This means that in less than a generation, digital media have radically transformed the way we inform and socialize, and that this transformation is still ongoing as older generations are gradually replaced by digital natives. From a scientific point of view, this transformation generates many phenomena to be studied, and even "unknown unknowns" whose effects will be revealed only with time.This roadmap covers the issues, impacts and future challenges of digital media as they relate to human well-being in the broadest sense, from mental health to the health of democracies.Its objective is to initiate a new interdisciplinary research community in this field, to define a research agenda, to formulate recommendations for future digital media policy and design, and to inspire future EU calls for projects to develop innovative and transdisciplinary research on these societal challenges.The roadmap is the result of the EU-funded project DIGEING conducted by an international consortium with the help of an interdisciplinary advisory group of international experts. Its writing was based on an hybrid methodology developped at CNRS and powered by GarganText, where the advisory group acted both as catalyst and guide for a larger collaborative mapping of the state-of-the-art and identification of challenges of that emerging field. More than forty researchers from fourteen European countries have contributed to the writing of this roadmap.This roadmap is complemented by online interactive maps that can be used by researchers to situate themselves in this evolving scientific landscape and by research funding agencies to launch new calls for projects