Apoptotic Bax at Oxidatively Stressed Mitochondrial Membranes: Lipid Dynamics and Permeabilization

0474912 - ÚFCH JH 2018 RIV US eng J - Journal Article
Dilgendein, A. P. - Pokorná, Šárka - Lidman, M. - Sparrman, T. - Šachl, Radek - Hof, Martin - Gröbner, G.
Apoptotic Bax at Oxidatively Stressed Mitochondrial Membranes: Lipid Dynamics and Permeabilization.
Biophysical Journal. Roč. 112, č. 10 (2017), s. 2147-2158. ISSN 0006-3495. E-ISSN 1542-0086
R&D Projects: GA ČR(CZ) GBP208/12/G016
Institutional support: RVO:61388955
Keywords : LOW-FREQUENCY MOTION * OXIDIZED PHOSPHOLIPIDS * BILAYER-MEMBRANES
OECD category: Physical chemistry
Impact factor: 3.495, year: 2017
Method of publishing: Open access

Mitochondria are crucial compartments of eukaryotic cells because they function as the cellular power plant and play a central role in the early stages of programmed cell death (apoptosis). To avoid undesired cell death, this apoptotic pathway is tightly regulated by members of the Bcl-2 protein family, which interact on the external surface of the mitochondria, i.e., the mitochondrial outer membrane (MOM), and modulate its permeability to apoptotic factors, controlling their release into the cytosol. A growing body of evidence suggests that the MOM lipids play active roles in this permeabilization process. In particular, oxidized phospholipids (OxPls) formed under intracellular stress seem to directly induce apoptotic activity at the MOM. Here we show that the process of MOM pore formation is sensitive to the type of OxPls species that are generated. We created MOM-mimicking liposome systems, which resemble the cellular situation before apoptosis and upon triggering of oxidative stress conditions. These vesicles were studied using 31P solid-state magic-angle-spinning nuclear magnetic resonance spectroscopy and differential scanning calorimetry, together with dye leakage assays. Direct polarization and cross-polarization nuclear magnetic resonance experiments enabled us to probe the heterogeneity of these membranes and their associated molecular dynamics. The addition of apoptotic Bax protein to OxPls-containing vesicles drastically changed the membranes’ dynamic behavior, almost completely negating the previously observed effect of temperature on the lipids’ molecular dynamics and inducing an ordering effect that led to more cooperative membrane melting. Our results support the hypothesis that the mitochondrion-specific lipid cardiolipin functions as a first contact site for Bax during its translocation to the MOM in the onset of apoptosis.
Permanent Link: http://hdl.handle.net/11104/0271819