Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Poster Abstracts

50-POS Board 25 The Role of Cardiolipins in Uncoupling Proteins 1/2 Functionalities Alessio Prunotto , Matteo Dal Peraro. École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Uncoupling Proteins (UCP) 1/2 are mitochondrial proteins that play a fundamental role in the energetic economy of this organelle. These proteins are actually designated to pump protons out of the inner mitochondrial matrix. As a matter of fact, for the generation of ATP, the cell necessitates to generate an electrochemical potential within the mitochondria, which is guaranteed by the electron transport chain, which accumulates protons inside the mitochondrial matrix. Such accumulation has to be dissipated by the UCP1 and UCP2, in order to prevent damages to the mitochondria functions. UCP1/2 are considered attractive targets for antidiabetes and antiobesity drugs. UCP2 has been solved by NMR. Based on this structure, we built the UCP1 using comparative modeling, thanks to the high identity between the two primary sequences (57%). The mechanism of action of these proteins is still largely unknown; for example, it is debated whether they assume a dimeric or tetrameric form, as well as how the transportation of protons is carried on. From this point of view, cardiolipins were proven to act as structure stabilizers and to enhance the proton transport activity of these proteins. Molecular Dynamics simulations of UCP1/2 were conducted at both atomistic and coarse-grain level, in order to understand the influence of the cardiolipins in the oligomerization state of these proteins. To assess this, we ran several simulations at different cardiolipins concentrations, in order to depict the consequences that the absence (or reduction) of this particular kind of lipid has on UCP1/2.

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