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The oxidized phospholipid PazePC promotes permeabilization of mitochondrial membranes by Bax
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SYSNO ASEP 0458493 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název The oxidized phospholipid PazePC promotes permeabilization of mitochondrial membranes by Bax Tvůrce(i) Lidman, M. (SE)
Pokorná, Šárka (UFCH-W) RID
Dingeldein, A. P. G. (SE)
Sparrman, T. (SE)
Wallgren, M. (SE)
Šachl, Radek (UFCH-W) RID, ORCID
Hof, Martin (UFCH-W) RID, ORCID
Gröbner, G. (SE)Zdroj.dok. Biochimica Et Biophysica Acta-Biomembranes. - : Elsevier - ISSN 0005-2736
Roč. 1858, č. 6 (2016), s. 1288-1297Poč.str. 10 s. Jazyk dok. eng - angličtina Země vyd. NL - Nizozemsko Klíč. slova Apoptosis ; Bax-protein ; Calorimetry Vědní obor RIV CF - Fyzikální chemie a teoretická chemie CEP GBP208/12/G016 GA ČR - Grantová agentura ČR Institucionální podpora UFCH-W - RVO:61388955 UT WOS 000375356900023 EID SCOPUS 84961771300 DOI 10.1016/j.bbamem.2016.03.003 Anotace Mitochondria play a crucial role in programmed cell death via the intrinsic apoptotic pathway, which is tightly regulated by the B-cell CLL/lymphoma-2 (Bcl-2) protein family. Intracellular oxidative stress causes the translocation of Bax, a pro-apoptotic family member, to the mitochondrial outer membrane (MOM) where it induces membrane permeabilization. Oxidized phospholipids (OxPls) generated in the MOM during oxidative stress directly affect the onset and progression of mitochondria-mediated apoptosis. Here we use MOM-mimicking lipid vesicles doped with varying concentrations of 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazePC), an OxPl species known to significantly enhance Bax-membrane association, to investigate three key aspects of Bax's action at the MOM: 1) induction of Bax pores in membranes without additional mediator proteins, 2) existence of a threshold OxPl concentration required for Bax-membrane action and 3) mechanism by which PazePC disturbs membrane organization to facilitate Bax penetration. Fluorescence leakage studies revealed that Bax-induced leakage, especially its rate, increased with the vesicles' PazePC content without any detectable threshold neither for OxPl nor Bax. Moreover, the leakage rate correlated with the Bax to lipid ratio and the PazePC content. Solid state NMR studies and calorimetric experiments on the lipid vesicles confirmed that OxPl incorporation disrupted the membrane's organization, enabling Bax to penetrate into the membrane. In addition, 15N cross polarization (CP) and insensitive nuclei enhanced by polarization transfer (INEPT) MAS NMR experiments using uniformly 15N-labeled Bax revealed dynamically restricted helical segments of Bax embedded in the membrane, while highly flexible protein segments were located outside or at the membrane surface. Pracoviště Ústav fyzikální chemie J.Heyrovského Kontakt Michaela Knapová, michaela.knapova@jh-inst.cas.cz, Tel.: 266 053 196 Rok sběru 2017
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