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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Poster Abstracts
89
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.