Fantastic beasts and how to find them—Molecular identification of the mitochondrial ATP-sensitive potassium channel

Despite reported sightings over many years, certain mitochondrial-specific channels have proven to be elusive beasts, evading molecular identification. However, combining modern genetics with a wave of their ion-sensing wand, researchers have managed to capture first the mitochondrial calcium uniporter, and now that semi-mythological beast, the mitochondrial ATP-sensitive potassium (mitoKATP) channel

A zenei nevelés helyzetének vizsgálata a füzesabonyi kistérség óvodáiban = Investigating music education in the pre-schools of the füzesabony region

A tanulmány az óvodai, illetve a családokban folyó zenei nevelés gyakorlati megvalósulásának vizsgálatával foglalkozik. Kutatásunkat a füzesabonyi kistérség négy óvodájában végeztük. Vizsgálatunk során a kérdőív, az interjú, a megfigyelés és a dokumentumelemzés módszerét alkalmaztuk. Az eredményekből kiderült, hogy a szülők sok esetben nincsenek tisztában az otthoni zenei nevelés helyes módszereivel, illetve a megfelelő, élményt nyújtó zenei nevelés esetenként az óvodákban sem valósul meg teljes mértékben. Kiderült továbbá, hogy a vizsgált óvodákban a szülők és az óvodapedagógusok közt a kapcsolattartás hiányosságokat mutat a zenei nevelés területén. = The study investigates the practical implementation of music education in kindergartens and families. Our research was carried out in four kindergartens of the Füzesabony small region. In the course of our research, we used the method of questionnaire, interview, observation, and document analysis. The results show that in many cases, parents are not aware of the correct methods of the home music education, and that appropriate, experiential music education is sometimes not fully implemented in kindergartens. It was also found that in the examined kindergartens, the communication between parents and kindergarten teachers shows shortcomings in the field of music education

PGC-1 family coactivators and cell fate: roles in cancer, neurodegeneration, cardiovascular disease and retrograde mitochondria-nucleus signalling.

Over the past two decades, a complex nuclear transcriptional machinery controlling mitochondrial biogenesis and function has been described. Central to this network are the PGC-1 family coactivators, characterised as master regulators of mitochondrial biogenesis. Recent literature has identified a broader role for PGC-1 coactivators in both cell death and cellular adaptation under conditions of stress, here reviewed in the context of the pathology associated with cancer, neurodegeneration and cardiovascular disease. Moreover, we propose that these studies also imply a novel conceptual framework on the general role of mitochondrial dysfunction in disease. It is now well established that the complex nuclear transcriptional control of mitochondrial biogenesis allows for adaptation of mitochondrial mass and function to environmental conditions. On the other hand, it has also been suggested that mitochondria alter their function according to prevailing cellular energetic requirements and thus function as sensors that generate signals to adjust fundamental cellular processes through a retrograde mitochondria-nucleus signalling pathway. Therefore, altered mitochondrial function can affect cell fate not only directly by modifying cellular energy levels or redox state, but also indirectly, by altering nuclear transcriptional patterns. The current literature on such retrograde signalling in both yeast and mammalian cells is thus reviewed, with an outlook on its potential contribution to disease through the regulation of PGC-1 family coactivators. We propose that further investigation of these pathways will lead to the identification of novel pharmacological targets and treatment strategies to combat disease

Organelles: The Emerging Signalling Chart of Mitochondrial Dynamics

Many molecular and functional details of single events in mitochondrial dynamics have been reported, but little is known about their coordination. A recent study describes how cellular Ca2+ signals, via remodelling the actin cytoskeleton, synchronise the formation of endoplasmic reticulum–mitochondria contacts with inner and outer mitochondrial membrane fission

ER-Mitochondria contact sites : a new regulator of cellular calcium flux comes into play

Endoplasmic reticulum (ER)-mitochondria membrane contacts are hotspots for calcium signaling. In this issue, Raturi et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201512077) show that the thioredoxin TMX1 inhibits the calcium pump SERCA2b at ER-mitochondria contact sites, thereby affecting ER-mitochondrial calcium transfer and mitochondrial bioenergetics

Annual Meeting of the International Society of Cancer Metabolism (ISCaM): Cancer Metabolism

Tumors are metabolic entities wherein cancer cells adapt their metabolism to their oncogenic agenda and microenvironmental influences. Metabolically different cancer cell subpopulations collaborate to optimize nutrient delivery with respect to immediate bioenergetic and biosynthetic needs. They can also metabolically exploit host cells. These metabolic networks are directly linked with cancer progression, treatment, resistance, and relapse. Conversely, metabolic alterations in cancer are exploited for anticancer therapy, imaging, and stratification for personalized treatments. These topics were addressed at the 4th annual meeting of the International Society of Cancer Metabolism (ISCaM) in Bertinoro, Italy, on 19–21 October 2017

Measurement of ATP in Single Oocytes: Impact of Maturation and Cumulus Cells on Levels and Consumption

Mitochondria provide the primary source of ATP in the oocyte and early embryo and mitochondrial dysfunction and deficit of mitochondria-derived ATP has been linked to suboptimal developmental competence. We have undertaken a study of ATP in the maturing mouse oocyte using a novel recombinant FRET based probe, AT1.03. We show that AT1.03 can be successfully used to monitor cytosolic ATP levels in single live oocytes over extended time periods. We find that ATP levels undergo dynamic changes associated with specific maturational events and that oocytes display altered rates of ATP consumption at different stages of maturation. Cumulus enclosed oocytes have a higher ATP level during maturation than denuded oocytes and this can be abolished by inhibition of gap junctional communication between the oocyte and cumulus cells. Our work uses a new approach to shed light on regulation of ATP levels and ATP consumption during oocyte maturation

Novel members of quinoline compound family enhance insulin secretion in RIN-5AH beta cells and in rat pancreatic islet microtissue

According to clinical data, some tyrosine kinase inhibitors (TKIs) possess antidiabetic effects. Several proposed mechanisms were assigned to them, however their mode of action is not clear. Our hypothesis was that they directly stimulate insulin release in beta cells. In our screening approach we demonstrated that some commercially available TKIs and many novel synthesized analogues were able to induce insulin secretion in RIN-5AH beta cells. Our aim was to find efficient, more selective and less toxic compounds. Out of several hits, we chose members from a compound family with quinoline core structure for further investigation. Here we present the studies done with these novel compounds and reveal structure activity relationships and mechanism of action. One of the most potent compounds (compound 9) lost its affinity to kinases, but efficiently increased calcium influx. In the presence of calcium channel inhibitors, the insulinotropic effect was attenuated or completely abrogated. While the quinoline TKI, bosutinib substantially inhibited tyrosine phosphorylation, compound 9 had no such effect. Molecular docking studies further supported our data. We confirmed that some TKIs possess antidiabetic effects, moreover, we present a novel compound family developed from the TKI, bosutinib and optimized for the modulation of insulin secretion