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Title [sv]
Bcl-2-proteinernas reglering av den mitokondriella apoptosen: de grundläggande mekanismerna och dessas beroende av protein-lipidinteraktioner
Title [en]
Regulation of Mitochondrial Apoptosis by Bcl-2 Proteins: Basic Mechanisms and their Dependence on Protein-Lipid Interactions
Abstract [sv]
The Bcl-2 family of proteins are central regulators of the intrinsic (mitochondrial) apoptosis pathway. Opposing members meet at the outer mitochondrial membrane, where they transmit a life or death signal. In case of a death signal membrane leakage will occur and the release of lethal apoptotic factors like cytochrome c. By using the anti-apoptotic Bcl-2 membrane protein and its counterpart, the pro-apoptotic Bax we will study this regulatory mechanism and its dependence on the mitochondrial membrane. In particular we will use biophysical and solid state NMR methods to i) study via affinity measurements the role of oxidative membrane damage (triggers apoptosis) on the recruitment of Bax to the membrane-embedded Bcl-2. ii) investigate the dependence of Bax-induced membrane leakage on Bcl-2 levels in vitro and in vivo. For this purpose we will compare the membrane integrity of intact normal v.s Bcl-2 enriched mitochondria upon Bax titration and compare itstudies of proteoliposomes containing increasing Bcl-2 levels;. iii) determine the structure of Bcl-2 protein upon its reconstitution into a lipid membrane environment. With this research we will generate basic knowledge about the membrane-associated molecular mechanisms used by the Bcl-2 protein family to regulate and execute apoptosis; and provide structural insight into the cell-protective function of the Bcl-2 membrane protein, a promising cancer drug target.
Principal InvestigatorGröbner, Gerhard
Coordinating organisation
Umeå University
Funder
Period
2014-01-01 － 2017-12-31
National Category
Physical ChemistryBiochemistry and Molecular BiologyBiophysics
Identifiers
DiVA, id: project:1363Project, id: 2013-05737_VR

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