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The oxidized phospholipid PazePC promotes permeabilization of mitochondrial membranes by Bax

SYSNO ASEP	0458493
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	The oxidized phospholipid PazePC promotes permeabilization of mitochondrial membranes by Bax
Author(s)	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)
Source Title	Biochimica Et Biophysica Acta-Biomembranes. - : Elsevier - ISSN 0005-2736 Roč. 1858, č. 6 (2016), s. 1288-1297
Number of pages	10 s.
Language	eng - English
Country	NL - Netherlands
Keywords	Apoptosis ; Bax-protein ; Calorimetry
Subject RIV	CF - Physical ; Theoretical Chemistry
R&D Projects	GBP208/12/G016 GA ČR - Czech Science Foundation (CSF)
Institutional support	UFCH-W - RVO:61388955
UT WOS	000375356900023
EID SCOPUS	84961771300
DOI	10.1016/j.bbamem.2016.03.003
Annotation	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.
Workplace	J. Heyrovsky Institute of Physical Chemistry
Contact	Michaela Knapová, michaela.knapova@jh-inst.cas.cz, Tel.: 266 053 196
Year of Publishing	2017

Number of the records: 1