Počet záznamů: 1
Apoptotic Bax at Oxidatively Stressed Mitochondrial Membranes: Lipid Dynamics and Permeabilization
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SYSNO ASEP 0474912 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Apoptotic Bax at Oxidatively Stressed Mitochondrial Membranes: Lipid Dynamics and Permeabilization Tvůrce(i) Dilgendein, A. P. (SE)
Pokorná, Šárka (UFCH-W) RID
Lidman, M. (SE)
Sparrman, T. (SE)
Šachl, Radek (UFCH-W) RID, ORCID
Hof, Martin (UFCH-W) RID, ORCID
Gröbner, G. (SE)Zdroj.dok. Biophysical Journal. - : Cell Press - ISSN 0006-3495
Roč. 112, č. 10 (2017), s. 2147-2158Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova LOW-FREQUENCY MOTION ; OXIDIZED PHOSPHOLIPIDS ; BILAYER-MEMBRANES Vědní obor RIV CF - Fyzikální chemie a teoretická chemie Obor OECD Physical chemistry CEP GBP208/12/G016 GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora UFCH-W - RVO:61388955 UT WOS 000402119300015 EID SCOPUS 85019768687 DOI 10.1016/j.bpj.2017.04.019 Anotace 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. Pracoviště Ústav fyzikální chemie J.Heyrovského Kontakt Michaela Knapová, michaela.knapova@jh-inst.cas.cz, Tel.: 266 053 196 Rok sběru 2018
Počet záznamů: 1