Influence of a mitochondrial genetic defect on capacitative calcium entry and mitochondrial organization in the osteosarcoma cells

AbstractEffects of T8993G mutation in mitochondrial DNA (mtDNA), associated with neurogenical muscle weakness, ataxia and retinitis pigmentosa (NARP), on the cytoskeleton, mitochondrial network and calcium homeostasis in human osteosarcoma cells were investigated. In 98% NARP and ρ0 (lacking mtDNA) cells, the organization of the mitochondrial network and actin cytoskeleton was disturbed. Capacitative calcium entry (CCE) was practically independent of mitochondrial energy status in osteosarcoma cell lines. The significantly slower Ca2+ influx rates observed in 98% NARP and ρ0, in comparison to parental cells, indicates that proper actin cytoskeletal organization is important for CCE in these cells

Projekt: Uniwersytet PAN

Among the scientific institutions in Poland, the institutes of the Polish Academy of Sciences possess top-ranking research potential. In the years 2013-2016, for instance, 19.7% of all research articles published in the most prestigious research journals for each particular field (the top 10% of the list of journals for each field, ranked by impact factor) by authors affiliated with Polish institutions came from the institutes of the Polish Academy of Sciences – this is far the best such percentage among all Polish academic institutions. The staff members at the PAS institutes are engaged not only in research, but also in teaching: as of 31 December 2016, there were 1607 individuals in regular PhD programs at the PAS institutes. Moreover, the degree of internationalization (8%) of these programs at the PAS institutes is the highest among all Polish higher-education institutions. These and other factors are seen as providing justification for the plan to pull together the potential of the PAS institutes in order to create a new higher-education institution, to be called the University of the Polish Academy of Sciences (UPAS), meant to become Poland’s first-ever research university. Plans call for UPAS to ultimately have a total of 2500 students studying in its programs, predominantly third-cycle (PhD-level) programs. Such a number will enable each student to be ensured individual supervision by top-notch researchers. It will also allow innovative teaching programs to be developed and tested in keeping with the new trends of the Internet era and e-learning, through online course offerings and through inter- and cross-disciplinary studies. Under this plan, UPAS stands a real chance of becoming a proud showpiece of Polish science and higher education: holding open, international competitions for various long-term positions as visiting professors, post-doc researchers, and PhD candidates will help further bolster the degree of internationalization among both the staff and students of UPAS, bringing it up to the level that characterizes the world’s best higher-education institutions. Given the size of Poland’s budget for science and higher education, attaining such a degree of internationalization in the near future will only be financially feasible for a university as small as UPAS. The above measures will also have a quality-boosting impact on the PAS institutes themselves, significantly improving their level. After several years, UPAS will stand a real chance of attaining very good standing in international rankings of the world’s higher education institutions, among the top 200 or even top 100 in the world. We should stress clearly: for this to happen, the funding for research at PAS institutes will need to be maintained on at least the same level as at present, the network of PAS institutes will need to be made more flexible, incorporating mechanisms generating significant synergy between the institutes (with UPAS as the common objective), and the project will need to be supported by a long-term program of internationalization of staff and students.Instytuty Polskiej Akademii Nauk mają wśród polskich instytucji naukowych czołowy potencjał merytoryczny. W instytutach PAN w latach 2013-2016 powstało 19,7% prac afiliowanych w polskich instytucjach i umieszczonych w najbardziej prestiżowych pismach naukowych danych dziedzin (górne 10% z list pism danej dziedziny nauki uszeregowanych według rosnącego współczynnika wpływu, IF). Jest to najlepszy wynik wśród polskich instytucji akademickich. Kadra instytutów PAN zajmuje się nie tylko badaniami, ale też dydaktyką; 1607 osób (stan na 31 grudnia 2016) było na stacjonarnych studiach doktoranckich w Instytutach PAN. Stopień umiędzynarodowienia studiów w PAN (8%) jest największy wśród polskich uczelni. W związku z tym uzasadnione wydaje się powołanie Uniwersytetu PAN (UPAN), który mógłby stać się pierwszą w Polsce uczelnią badawczą. Planuje się, że docelowo kształciłoby się na nim 2,5 tys. osób, w przeważającej części studentek i studentów III stopnia. Taka liczba pozwoli na zagwarantowanie indywidualnej merytorycznej opieki każdemu studentowi, a także na wprowadzenie i przetestowanie nowatorskich programów dydaktycznych, właściwych erze Internetu i e-learningu, prowadzenia studiów online poprzez courser, studiów inter- i crossdyscyplinarnych. UPAN ma realne szanse stać się wizytówką polskiej nauki i szkolnictwa wyższego, gdyż otwarte, międzynarodowe wieloletnie programy konkursowe na pozycje: wizytujących profesorów, stażystów podoktorskich i doktorantów mogą podnieść umiędzynarodowienie zarówno kadry, jak i studentów UPAN do poziomu właściwego najlepszym uczelniom świata. Z uwagi na wielkość naszego budżetu nauki i szkolnictwa wyższego osiągnięcie takiego umiędzynarodowienia jest finansowo realne w najbliższym czasie tylko dla uczelni tak małej jak UPAN. Opisane działania będą projakościowe także dla samych instytutów PAN i istotnie podniosą ich poziom merytoryczny. Po kilku latach UPAN ma realne szanse na uplasowanie się w międzynarodowych rankingach na bardzo dobrych pozycjach, w pierwszej dwusetce, a nawet w pierwszej setce najlepszych światowych uczelni. Należy podkreślić, że warunkiem tego jest zapewnienie finansowania badań w instytutach PAN na co najmniej takim jak obecnie poziomie, uelastycznienie ich sieci, wytworzenie mechanizmów synergii pomiędzy instytutami (wspólny cel – UPAN) oraz wsparcie tego projektu długoletnim programem umiędzynarodowienia kadry i studentów

Pandemic chronicles 2020-2021

Kroniki pandemii to zbiór 27 stanowisk opublikowanych przez interdyscyplinarny Zespół doradczy ds. COVID-19 przy Prezesie Polskiej Akademii Nauk, działający od lipca 2020 roku. Jest to już drugie po Zrozumieć COVID-19 obszerniejsze opracowanie naszego zespołu porządkujące wiadomości dotyczące wirusa SARS-CoV-2 i powodowanej przez niego choroby COVID-19. Wydane we wrześniu 2020 roku Zrozumieć COVID-19 miało na celu podsumowanie przebiegu pierwszych miesięcy pandemii i przygotowanie społeczeństwa w Polsce do ciężkiego sezonu jesienno-zimowego 2020/2021. Niniejsze opracowanie powstaje po dwóch latach trwania pandemii, która rozpoczęła się w Wuhan w grudniu 2019 roku. Mamy nadzieję, że dzięki na bieżąco tworzonym tekstom raportującym przebieg pandemii i dylematy, przed którymi stawało społeczeństwo, w przypadku kolejnych podobnych wyzwań skorzystamy z tych trudnych i ważnych doświadczeń

The apparent non-linearity of the relationship between the rate of respiration and the protonmotive force of mitochondria can be explained by heterogeneity of mitochondrial preparations

AbstractThe apparent non-linear relationship between the rate of respiration and the protonmotive force in mitochondria under resting state conditions is an observation which has led to concepts such as (i) non-chute characteristics of the proton leak through the mitochondrial membrane, or (ii) a slippage of proton pumps. We propose that this non-linearity may be a consequence of a heterogeneity of isolated mitochondria concerning the degree of coupling, since a small proportion of totally uncoupled, or loosely coupled, organelles may considerably contribute to the total respiration but not, or only slightly, to the protonmotive force. This hypothesis is supported by a fairly good fitting of computed relationships with those determined experimentally

Calcium Signals Are Affected by Ciprofloxacin as a Consequence of Reduction of Mitochondrial DNA Content in Jurkat Cells

The effects of ciprofloxacin on mitochondrial DNA (mtDNA) content, oxygen consumption, mitochondrial membrane potential, cellular ATP formation, and capacitative Ca(2+) entry into Jurkat cells were investigated. In cells incubated for several days with 25 μg/ml ciprofloxacin, a 60% reduction of mtDNA content, inhibition of the respiratory chain, and a significant decrease in mitochondrial membrane potential were observed. These changes led to a decrease in the calcium buffering capacity of mitochondria which, in turn, resulted in a gradual inhibition of the capacitative Ca(2+) entry. On days 4, 7, and 11 of incubation with ciprofloxacin, the initial rates of Ca(2+) entry were reduced by 33%, 50%, and 50%, respectively. Ciprofloxacin caused a transient decrease in the cellular capability for ATP formation. In cells incubated for 15 min with glucose, pyruvate, and glutamine as exogenous fuel, ciprofloxacin reduced ATP content by 16% and 35% on days 4 and 7, respectively, of incubation with the drug. However, on day 11 of incubation with ciprofloxacin, a recovery of cellular ATP formation was observed. In conclusion, long-term exposure of Jurkat cells to ciprofloxacin at a concentration of 25 μg/ml seriously affects cellular energy metabolism and calcium homeostasis

In memory of Professor Lech Wojtczak, researcher and person

Professor Lech Wojtczak spent his entire scientific life at the Nencki Institute of Experimental Biology PAS, where he worked since 1947. He is the author or co-author of two hundred scientific papers, promoted 15 doctors of science, was the Full Member of PAS and has been awarded with several prizes and honors. Among his students are three successive directors of the Nencki Institute, the authors of the present article. Scientific interests of Professor Lech Wojtczak were always dealing with bioenergectics, a discipline that he led in Poland and Eastern-Central Europe. In particular, his studies focused on the role of fatty acids and their derivatives on bioenergetics, on the regulatory role of surface potential of biomembranes on enzymatic and transport activities, on the regulatory role of calcium and magnesium in mitochondria, on the role of free oxigen radicals in bioenergetics, etc. Apart from being a great scientist, Lech Wojtczak was also a fantastic teacher, and an excellent scientific supervisor. Being well recognized in the world, he was placing members of his research group in foreign laboratories, as well as was sending tchem to courses and conferences. This was opening their minds to the world, and to other cultures, and allowed Lech Wojtczak to form from his collaborators the next generation of good scientists and future leaders. The list of the most important pupils of Professor Wojtczak is given in the article. Lech was also excellent in social contacts, and in creating a friendly atmosphere. Together with his wife Anna, they kept an open home, often inviting collaborators to parties that usually led to long scientific discussions. With the sudden death of Pofessor Lech Wojtczak Polish science suffered a great loss. This eminent researcher, the father of Polish bioenergetics, but also a warm and modest person, will be dearly missed

Participation of phospholipase A2 isoforms in the control of calcium influx into electrically non-excitable cells

The participation of phospholipase A2 isoforms in capacitative store-operated Ca2+ influx into Jurkat leukemic T and MDCK cells was investigated. Preincubation of Jurkat cells with either bromophenacyl bromide (an inhibitor of secreted phospholipase A2, sPLA2) or Helss (an inhibitor of calcium independent phospholipase A2 - iPLA2) resulted in a significant inhibition of the calcium influx. The extent of this inhibition depended on the pH of the extracellular millieu; it increased with alkalisation. The rate of Ca2+ influx into MDCK cells was reduced by bromophenacyl bromide. Preincubation of these cells with Helss resulted in the stimulation of the influx. These observations suggest the participation of different PLA2 isoforms in the regulation of Ca2+ influx. They also show that the extent that PLA2 isoforms control the influx depends on the pH of the medium. Finally, these data indicate that various phospholipase A2 isoforms may play a role in the control of Ca2+ influx in different cell lines