Partner: Prof. Jerzy Duszyński, Ph.D., Dr. Habil.

Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)

Recent publications
1.Walczak J., Dębska-Vielhaber G., Vielhaber S., Szymański J., Charzyńska A., Duszyński J., Szczepanowska J., Distinction of sporadic and familial forms of ALS based on mitochondrial characteristics, The FASEB Journal, ISSN: 0892-6638, DOI: 10.1096/fj.201801843R, Vol.33, No.3, pp.4388-4403, 2019
Abstract:

Bioenergetic failure, oxidative stress, and changes in mitochondrial morphology are common pathologic hallmarks of amyotrophic lateral sclerosis (ALS) in several cellular and animal models. Disturbed mitochondrial physiology has serious consequences for proper functioning of the cell, leading to the chronic mitochondrial stress. Mitochondria, being in the center of cellular metabolism, play a pivotal role in adaptation to stress conditions. We found that mitochondrial dysfunction and adaptation processes differ in primary fibroblasts derived from patients diagnosed with either sporadic or familial forms of ALS. The evaluation of mitochondrial parameters such as the mitochondrial membrane potential, the oxygen consumption rate, the activity and levels of respiratory chain complexes, and the levels of ATP, reactive oxygen species, and Ca2+ show that the bioenergetic properties of mitochondria are different in sporadic ALS, familial ALS, and control groups. Comparative statistical analysis of the data set (with use of principal component analysis and support vector machine) identifies and distinguishes 3 separate groups despite the small number of investigated cell lines and high variability in measured parameters. These findings could be a first step in development of a new tool for predicting sporadic and familial forms of ALS and could contribute to knowledge of its pathophysiology.—Walczak, J., Dębska-Vielhaber, G., Vielhaber, S., Szymański, J., Charzyńska, A., Duszyński, J., Szczepanowska, J. Distinction of sporadic and familial forms of ALS based on mitochondrial characteristics.

Keywords:

amyotrophic lateral sclerosis, neurodegeneration, primary fibroblasts, PCA

Affiliations:
Walczak J.-other affiliation
Dębska-Vielhaber G.-Otto-von-Guericke University, Magdeburg (DE)
Vielhaber S.-Otto-von-Guericke University, Magdeburg (DE)
Szymański J.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Charzyńska A.-University of Warsaw (PL)
Duszyński J.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Szczepanowska J.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
2.Malińska D., Więckowski M.R., Michalska B., Drabik K., Prill M., Patalas-Krawczyk P., Walczak J., Szymański J., Mathis C., Van der Toorn M., Luettich K., Hoeng J., Peitsch M.C., Duszyński J., Szczepanowska J., Mitochondria as a possible target for nicotine action, Journal of Bioenergetics and Biomembranes, ISSN: 0145-479X, DOI: 10.1007/s10863-019-09800-z, Vol.51, No.4, pp.259-276, 2019
Abstract:

Mitochondria are multifunctional and dynamic organelles deeply integrated into cellular physiology and metabolism. Disturbances in mitochondrial function are involved in several disorders such as neurodegeneration, cardiovascular diseases, metabolic diseases, and also in the aging process. Nicotine is a natural alkaloid present in the tobacco plant which has been well studied as a constituent of cigarette smoke. It has also been reported to influence mitochondrial function both in vitro and in vivo. This review presents a comprehensive overview of the present knowledge of nicotine action on mitochondrial function. Observed effects of nicotine exposure on the mitochondrial respiratory chain, oxidative stress, calcium homeostasis, mitochondrial dynamics, biogenesis, and mitophagy are discussed, considering the context of the experimental design. The potential action of nicotine on cellular adaptation and cell survival is also examined through its interaction with mitochondria. Although a large number of studies have demonstrated the impact of nicotine on various mitochondrial activities, elucidating its mechanism of action requires further investigation.

Keywords:

adaptation, mitochondria, nicotine, oxidative stress

Affiliations:
Malińska D.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Więckowski M.R.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Luettich K.-Philip Morris Products S.A. (CH)
Hoeng J.-Philip Morris Products S.A. (CH)
Peitsch M.C.-Philip Morris Products S.A. (CH)
Duszyński J.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Szczepanowska J.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Michalska B.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Drabik K.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Prill M.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Patalas-Krawczyk P.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Walczak J.-other affiliation
Szymański J.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Mathis C.-Philip Morris Products S.A. (CH)
Van der Toorn M.-Philip Morris Products S.A. (CH)
3.Malińska D., Szymański J., Patalas-Krawczyk P., Michalska B., Wojtala A., Prill M., Partyka M., Drabik K., Walczak J., Sewer A., Johne S., Luettich K., Peitsch M.C., Hoeng J., Duszyński J., Szczepanowska J., van der Toorn M., Więckowski M.R., Assessment of mitochondrial function following short- and long-term exposure of human bronchial epithelial cells to total particulate matter from a candidate modified-risk tobacco product and reference cigarettes, Food and Chemical Toxicology, ISSN: 0278-6915, DOI: 10.1016/j.fct.2018.02.013, Vol.115, pp.1-12, 2018
Abstract:

Mitochondrial dysfunction caused by cigarette smoke is involved in the oxidative stress-induced pathology of airway diseases. Reducing the levels of harmful and potentially harmful constituents by heating rather than combusting tobacco may reduce mitochondrial changes that contribute to oxidative stress and cell damage. We evaluated mitochondrial function and oxidative stress in human bronchial epithelial cells (BEAS 2B) following 1- and 12-week exposures to total particulate matter (TPM) from the aerosol of a candidate modified-risk tobacco product, the Tobacco Heating System 2.2 (THS2.2), in comparison with TPM from the 3R4F reference cigarette. After 1-week exposure, 3R4F TPM had a strong inhibitory effect on mitochondrial basal and maximal oxygen consumption rates compared to TPM from THS2.2. Alterations in oxidative phosphorylation were accompanied by increased mitochondrial superoxide levels and increased levels of oxidatively damaged proteins in cells exposed to 7.5 μg/mL of 3R4F TPM or 150 μg/mL of THS2.2 TPM, while cytosolic levels of reactive oxygen species were not affected. In contrast, the 12-week exposure indicated adaptation of BEAS-2B cells to long-term stress. Together, the findings indicate that 3R4F TPM had a stronger effect on oxidative phosphorylation, gene expression and proteins involved in oxidative stress than TPM from the candidate modified-risk tobacco product THS2.2.

Keywords:

Mitochondria, Mitochondrial respiratory chain, Oxidative stress, BEAS-2B cells, Cigarette, Tobacco heating system

Affiliations:
Malińska D.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Szymański J.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Johne S.-Philip Morris Products S.A. (CH)
Luettich K.-Philip Morris Products S.A. (CH)
Peitsch M.C.-Philip Morris Products S.A. (CH)
Hoeng J.-Philip Morris Products S.A. (CH)
Duszyński J.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Szczepanowska J.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
van der Toorn M.-Philip Morris Products S.A. (CH)
Więckowski M.R.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Patalas-Krawczyk P.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Michalska B.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Wojtala A.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Prill M.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Partyka M.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Drabik K.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Walczak J.-other affiliation
Sewer A.-Philip Morris Products S.A. (CH)
4.Walczak J., Partyka M., Duszyński J., Szczepanowska J., Implications of mitochondrial network organization in mitochondrial stress signalling in NARP cybrid and Rho0 cells, Scientific Reports, ISSN: 2045-2322, DOI: 10.1038/s41598-017-14964-y, Vol.7, No.14864, pp.1-14, 2017
Abstract:

Mitochondrial dysfunctions lead to the generation of signalling mediators that influence the fate of that organelle. Mitochondrial dynamics and their positioning within the cell are important elements of mitochondria-nucleus communication. The aim of this project was to examine whether mitochondrial shape, distribution and fusion/fission proteins are involved in the mitochondrial stress response in a cellular model subjected to specifically designed chronic mitochondrial stress: WT human osteosarcoma cells as controls, NARP cybrid cells as mild chronic stress and Rho0 as severe chronic stress. We characterized mitochondrial distribution in these cells using confocal microscopy and evaluated the level of proteins directly involved in the mitochondrial dynamics and their regulation. We found that the organization of mitochondria within the cell is correlated with changes in the levels of proteins involved in mitochondrial dynamics and proteins responsible for regulation of this process. Induction of the autophagy/mitophagy process, which is crucial for cellular homeostasis under stress conditions was also shown. It seems that mitochondrial shape and organization within the cell are implicated in retrograde signalling in chronic mitochondrial stress.

Affiliations:
Walczak J.-other affiliation
Partyka M.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Duszyński J.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Szczepanowska J.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
5.Rowiński P.M., Burczyński T., Duszyński J., Rychard A., Uniwersytet badawczy, czyli…?, NAUKA, ISSN: 1231-8515, Vol.3, pp.35-56, 2017
6.Duszyński J., Burczyński T., Rowiński P.M., Rychard A., Projekt: Uniwersytet PAN, Nauka i Szkolnictwo Wyższe, ISSN: 1231-0298, Vol.2, No.50, pp.59-76, 2017
Abstract:

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.

Keywords:

research university, University of the Polish Academy of Sciences, excellence in science

Affiliations:
Duszyński J.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Burczyński T.-IPPT PAN
Rowiński P.M.-Polish Academy of Science (PL)
Rychard A.-Institute of Philosophy and Sociology, Polish Academy of Sciences (PL)
7.Wojewoda M., Walczak J., Duszyński J., Szczepanowska J., Selenite activates the ATM kinase-dependent DNA repair pathway in human osteosarcoma cells with mitochondrial dysfunction, Biochemical Pharmacology, ISSN: 0006-2952, DOI: 10.1016/j.bcp.2015.03.016, Vol.95, No.3, pp.170-176, 2015
Abstract:

Mitochondrial dysfunction and reactive oxygen species (ROS) induced oxidative damage are implicated in the pathogenesis of several human diseases. Based on our previous findings that ROS level was higher in human osteosarcoma cybrids—Neuropathy, Ataxia and Retinitis Pigmentosa (NARP) and was reduced by selenite treatment, this study was designed to elucidate the effects of selenite administration on oxidative and nitrosative damage to lipids, proteins and DNA.

Oxidative and nitrosative damage to lipids and proteins was not increased in NARP cybrids or mitochondrial DNA-lacking Rho0 cells (displaying mitochondrial dysfunction) when compared with control WT cells. However, we found the enhanced formation of DNA double-strand breaks based on the level of histone γH2AX (phosphorylated at Ser 139), which is known to be phosphorylated by ATM (Ataxia Telangiectasia Mutated) kinase in response to DNA damage. Selenite increased the activity of ATM kinase in NARP cybrids and Rho0 cells without concomitant increase in levels of histone γH2AX.

Activation of the ATM kinase-dependent DNA repair pathway triggered by selenite could not be associated with enhanced DNA damage but might rather result from selenite-induced activation of ATM-dependent DNA repair mechanisms which could account for protective effects of this agent.

Keywords:

Mitochondrial dysfunction, Selenite, DNA repair, ATM kinase, Oxidative damage

Affiliations:
Wojewoda M.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Walczak J.-other affiliation
Duszyński J.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Szczepanowska J.-Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)