Head of laboratory
Research profile
Research carried by our laboratory is focused on mitochondrial physiology. We are investigating the relations between mitochondrial bioenergetics and oxidative stress in several pathological situations. Especially, we intend to disclose the hepatic redox alterations and the specific end-points for mitochondrial dysfunction, which drive the progression of Non-Alcoholic Fatty Liver Disease (NAFLD). We addresses many conceptually exciting and fundamental questions, such as: a) what are the molecular mechanisms underlying NAFLD progression? or b) is there a possibility by modulating oxidative stress to protect against or slow down development or the progression of NAFLD? Moreover, we are investigating the molecular composition and role in cellular physiology and pathology of the mitochondria-associated membranes (MAMs) that are physical platforms enabling communication between mitochondria and endoplasmic reticulum. The proteins and enzymes localized in MAMs are involved in several crucial processes and can impact cell metabolism and the cell fate. Another line of research conducted in the laboratory is the investigation of the precise molecular composition of the mitochondrial Permeability Transition Pore (mPTP), which despite the intense experimental interest throughout the last two decades still remains elusive. The precise knowledge of the structure, mode of action and regulators of PTPC is lacking and this constitutes a substantial obstacle in the development of mPTP-targeting agents with clinical applications.
For further information visit: https://wieckowski-mitolab.nencki.edu.pl
Current research activities
- investigation the role of mitochondrial dysfunction in the development and progression of nonalcoholic fatty liver disease
- evaluation of the mitochondrial dysfunction and the status of oxidative stress in metabolic disorders
- investigation of the impact of p66Shc protein on the mitochondrial metabolism and oxidative stress in tumors
- studies of mitochondria associated membranes as a important platform enabling the cross talk between mitochondria and endoplasmic reticulum
- investigation of the molecular composition of the mitochondrial permeability transition pore
Selected Publications
Rimessi A, Pozzato C, Carparelli L, Rossi A, Ranucci S, De Fino I, Cigana C, Talarico A, Wieckowski MR, Ribeiro CMP, Trapella C, Rossi G, Cabrini G, Bragonzi A, Pinton P. (2020) Pharmacological modulation of mitochondrial calcium uniporter controls lung inflammation in cystic fibrosis. Science Advances. 6(19): eaax9093.
Simoes ICM, Morciano G, Lebiedzinska-Arciszewska M, Aguiari G, Pinton P, Potes Y, Wieckowski MR. (2020) The mystery of mitochondria-ER contact sites in physiology and pathology: A cancer perspective. Biochim. Biophys. Acta Mol. Basis Dis. 1866(10): 165834.
Bonora M, Wieckowski MR, Sinclair DA, Kroemer G, Pinton P, Galluzzi L. (2019) Targeting mitochondria for cardiovascular disorders: therapeutic potential and obstacles. Nat. Rev. Cardiol. 16(1): 33-55.
Malik AN, Simões ICM, Rosa HS, Khan S, Karkucinska-Wieckowska A, Wieckowski MR. (2019) A Diet Induced Maladaptive Increase in Hepatic Mitochondrial DNA Precedes OXPHOS Defects and May Contribute to Non-Alcoholic Fatty Liver Disease. Cells. 8(10):1222.
Bonora M, Morganti C, Morciano G, Pedriali G, Lebiedzinska-Arciszewska M, Aquila G, Giorgi C, Rizzo P, Campo G, Ferrari R, Kroemer G, Wieckowski MR, Galluzzi L, Pinton P. (2017) Mitochondrial permeability transition involves dissociation of F1FO ATP synthase dimers and C-ring conformation. EMBO Rep. 18(7): 1077-1089.