Mitochondrial dysfunction associated oxidative stress

We study a contribution of mitochondrial respiratory chain components to ROS production and metabolism in following models: cells derived from patients with genetic mitochondrial disorders and aging mice. We are also interested in mitochondrial aspects of tumors and pharmacological toxicity corresponding to mitochondria.

We investigate the role of mitochondrial Ca²⁺ handling in vivo and its relevance to the mitochondrial dysfunction and ageing processes, especially the role of MAM (mitochondria associated membranes) and PAM (plasma membrane associated membranes) fractions. We biochemically characterized the MAM and PAM fractions. We have shown that p66Shc, a life span regulator protein is also enriched in MAM fraction of old animals. We attempt to elucidate the molecular composition of mitochondrial permeability transition pore. Isolation and purification of mitochondrial contact sites.

Mitochondrial function in cells with disturbed glycogen metabolism

Our research interests include the interactions between mitochondria and other components of cellular energy metabolism, such as glycolysis and glycogen metabolism. Glycogen is a branched polymer of glucose moieties, used as an intracellular store of glucose. Its hydrolysis ensures the supply of energy substrates for glycolysis during times of short starvation or temporarily increased energy expenditure in the cell. Being involved in ATP synthesis, glycogen metabolism is under control of multiple regulatory mechanisms, adjusting the intensity of anabolic and catabolic processes to the energetic needs of the cell and to the substrate availability. Thus, disturbances in glycogen metabolism may affect other processes responsible for ATP synthesis, including mitochondrial oxidative phosphorylation and overall mitochondrial function.

Our current research focuses on disturbances in intracellular energy metabolism accompanying the glycogen storage disease type IV (GSD IV). It is a genetic disease associated to partial deficiency of glycogen branching enzyme, which leads to accumulation of improperly structured, poorly branched glycogen. Applying different biochemical methods (measurements of enzymes and metabolites levels, immunocytochemistry, mitochondrial functional tests), we investigate, at the cellular level, the influence of improper glycogen structure on signaling pathways regulating energy metabolism and, in consequence, on other bioenergetic processes. We also try to define the mechanisms responsible for cell injuries observed in GSD IV, in particular the type of the cellular stress accompanying the disease (mechanical damage, energetic stress etc.).

Funding

MNiSW „Rola białka tau oraz jego fosforylacji w regulacji indukowanej przez białko prionowe oligomeryzacji tubuliny” (2010-2013)

HFSP „The dark side of a bright molecule: Determinants of glycogen-induced cell dysfunction” (2011 - 2014)

NCN „Rola mitochondriów w zaburzeniach różnicowania prekursorów oligodendrocytów” (2011-2014)

„Ciemne strony pożytecznej cząsteczki – podłoże związanych z glikogenem zmian patologicznych” – projekt międzynarodowy współfinansowany, MNiSW nr W100/HFSC/2011 (2011 - 2014)

FCT “Role of mitochondrial p66Shc  in drug-induced mitochondrial toxicity memory” (2013-2014)

MNiSW „Juventus Plus” „Udział białek rozprzęgających w regulacji poziomu reaktywnych form tlenu-nowe spojrzenie na ochronę antyoksydacyjną” (2011-2013)

NCN (Opus) „Metabolizm energetyczny komórek z glikogenozą typu IV” (2012-2015)

NCN (Opus2) „Wpływ ortopokswirusa ektromelii na mitochondria permisywnych komórek RAW 264.7 i L929: badania in vivo” (2012-2015)

NCBiR „Od mitochondriów do innowacyjnych kosmetyków o działaniu protekcyjnym” (2012-2015)

Grant NCN Harmonia, UMO-2013/08/M/NZ3/00707 „Stres mitochondrialny; rola dynamiki mitochondriów we wstecznej kaskadzie sygnałowej w fibroblastach pochodzących od pacjentów z rozpoznaną choroba neurodegeneracyjną” (2013-2016)