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Mitochondrial Membrane Model

Biomembranes are an essential part of all living organisms. They are structured, well-regulated lipid bilayers that are not only borders of the cellular compartment itself but also of the organelles within the cell. Biomembranes are of a dynamic nature; they undergo permanent changes and are a functional part of the cell. The cell controls processes that affect both (1) the outside appearance of the membrane, such as the formation of vesicles, fusion, fission and invagination, which can be tracked using microscopes, as well as (2) the inner membrane structure, e.g., lipid composition, formation of lipid rafts and lipid asymmetry (i.e., the unequal distribution of lipids between the two membrane monolayers).

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Besides other factors, the outlined dynamics of membranes are due to interactions between membrane proteins and lipids. At our Department, we especially focus on the interaction of pro-apoptotic BCL-2 proteins and the outer mitochondrial membrane, which becomes permeable in the course of this interaction and can therefore be regarded a key player in the process of apoptosis. Liposomes are used as an in-vitroouter mitochondrial membrane model system for simulating these processes (Martin Holzer, PhD thesis by Michael Keller). Especially interactions of specific lipids with the hydrophobic domains of relevant proteins play a major role in this context.

Another key aspect in this research project is toinvestigate the lipid asymmetry of the mammalian outer mitochondrial membrane. Regulation of lipid asymmetry is supposed to be a mechanism of controlling the apoptotic processes described before. To this end, protocols for the preparative isolation of mitochondria of high purity via free-flow electrophoreses are developed. These purified mitochondria are subject to special methods designed for the determination of asymmetrical lipid distribution, which comprise e.g., the use of HPTLC analyses and the development of new HPLC methods for the quantification of lipids after separation in different lipid classes.

Funding
The project was funded between 2010 and 2011by the Cluster of Excellence "BIOSS Centre for Biological Signalling Studies" (DFG EXC 294), .

 

 

 

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