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Project type
Znanstveno-istraživački projekti
Programme
Installation Research Projects
Financier
Croatian Science Foundation
Start date
Sep 1st 2015
End date
Jan 9th 2018
Status
Done
Total cost
589000 HRK
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The proposed project aims to unravel the molecular details of the processes connected with proton transfer and oxidative stress in mitochondria, organelles located in cells which convert oxygen and external energy supply into adenosine triphosphate (ATP) in the process of oxidative phosphorylation. During this process, a delicate energy balance is maintained between pumping of protons outside the inner mitochondrial membrane by the electron-transport chain proteins and transferring them back inside in the process of ATP synthesis by the ATP synthase. This balance is not always optimal and a special class of membrane proteins located inside inner mitochondrial membranes, called uncoupling proteins, serves as a control of the proton transfer rate through the membrane. Particular attention will be paid to the study of the reactivity of various reactive aldehydes generated during oxidative stress within phospholipid bilayers, towards uncoupling proteins. These deleterious reactions enhance the activity of uncoupling proteins resulting in the increased proton leak through inner mitochondrial membrane which in turn modifies energy balance inside the cell leading to various harmful diseases, such as cancer, type 2 diabetes and obesity. The project application uses the ''state of the art'' computational approach by combining quantum chemical calculations and molecular dynamics simulations. Also, the theoretical work is expanded with the experimental work where model compounds will be synthesized and used in model reaction systems to further understand and cross-check the simulation results. The research will endorse health by providing the community better understanding of the underlying principles and mechanisms by which deleterious aldehydes react with uncoupling proteins. The novel ideas will be proposed in order to better understand the function of uncoupling proteins, to develop drugs for improving health and to minimize effects due to oxidation processes.

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