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Title [sv]
Organisation av mitokondriemembraner under oxidativ stress - deras aktiva roll i regleringen av apoptos.
Title [en]
Organization of mitochondrial membranes under oxidative stress: Implications for their active role in regulation of apoptosis.
Abstract [en]
The mitochondrial membrane system plays a key role in the regulation of programmed cell death (apoptosis) by the Bcl-2 protein family. In the intrinsic apoptotic pathway opposing - apoptotic versus pro-survival - members of this protein family meet at the mitochondrial surface, namely the mitochondrial outer membrane (MOM), where they arbitrate a life or death sentence. In case of a death verdict as a consequence of elevated intracellular oxidative stress, the apoptotic Bax protein is recruited to the MOM where it induces permeabilization of its target membrane and release of apoptotic factors such as cytochrome c. By using neutron reflectometry as our main method (and solid state NMR complimentary) we will provide atomic-level insight into the structural and dynamic organization of these membranes under oxidative stress conditions prior and upon the presence of membrane-active Bax protein. In particular we will investigate i) the dependence of membrane architecture on degree and type of oxidized lipids (OxPls) present and ii) changes induced by the presence of Bax and  their correlation with the formed lipid-Bax complexes. With this research we will generate fundamental knowledge about the molecular features of the MOM necessary to enable the Bcl-2 protein family to regulate and execute apoptosis upon onset of apoptosis through oxidative stress; information also useful for novel cancer strategies.
Principal InvestigatorGröbner, Gerhard
Coordinating organisation
Umeå University
Funder
Period
2017-01-01 － 2020-12-31
National Category
Physical ChemistryBiophysics
Identifiers
DiVA, id: project:1505Project, id: 2016-06963_VR

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