-
Something wrong with this record ?
The oxidized phospholipid PazePC promotes permeabilization of mitochondrial membranes by Bax
M. Lidman, Š. Pokorná, AP. Dingeldein, T. Sparrman, M. Wallgren, R. Šachl, M. Hof, G. Gröbner,
Language English Country Netherlands
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Calorimetry, Differential Scanning MeSH
- Phosphorylcholine analogs & derivatives metabolism MeSH
- Humans MeSH
- Carbon-13 Magnetic Resonance Spectroscopy MeSH
- Mitochondrial Membranes metabolism MeSH
- Oxidation-Reduction MeSH
- Permeability MeSH
- bcl-2-Associated X Protein metabolism MeSH
- Proton Magnetic Resonance Spectroscopy MeSH
- Unilamellar Liposomes MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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 (15)N-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.
Department of Biochemistry Charles University Hlavova 8 128 40 Prague 2 Czech Republic
Department of Chemistry University of Umeå SE 901 87 Umeå Sweden
Department of Medical Chemistry and Biophysics University of Umeå SE 901 87 Umeå Sweden
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc16027606
- 003
- CZ-PrNML
- 005
- 20170124161441.0
- 007
- ta
- 008
- 161005s2016 ne f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.bbamem.2016.03.003 $2 doi
- 024 7_
- $a 10.1016/j.bbamem.2016.03.003 $2 doi
- 035 __
- $a (PubMed)26947183
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a ne
- 100 1_
- $a Lidman, Martin $u Department of Chemistry, University of Umeå, SE-901 87 Umeå, Sweden.
- 245 14
- $a The oxidized phospholipid PazePC promotes permeabilization of mitochondrial membranes by Bax / $c M. Lidman, Š. Pokorná, AP. Dingeldein, T. Sparrman, M. Wallgren, R. Šachl, M. Hof, G. Gröbner,
- 520 9_
- $a 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 (15)N-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.
- 650 _2
- $a diferenciální skenovací kalorimetrie $7 D002152
- 650 _2
- $a magnetická rezonanční spektroskopie s uhlíkem 13C $7 D066241
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a mitochondriální membrány $x metabolismus $7 D051336
- 650 _2
- $a oxidace-redukce $7 D010084
- 650 _2
- $a permeabilita $7 D010539
- 650 _2
- $a fosforylcholin $x analogy a deriváty $x metabolismus $7 D010767
- 650 _2
- $a protonová magnetická rezonanční spektroskopie $7 D066244
- 650 _2
- $a unilamelární lipozómy $7 D053835
- 650 _2
- $a protein X asociovaný s bcl-2 $x metabolismus $7 D051028
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Pokorná, Šárka $u J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v. v. i., Dolejškova 3, 182 23 Prague 8, Czech Republic; Department of Biochemistry, Charles University, Hlavova 8, 128 40 Prague 2, Czech Republic.
- 700 1_
- $a Dingeldein, Artur P G $u Department of Chemistry, University of Umeå, SE-901 87 Umeå, Sweden.
- 700 1_
- $a Sparrman, Tobias $u Department of Chemistry, University of Umeå, SE-901 87 Umeå, Sweden.
- 700 1_
- $a Wallgren, Marcus $u Department of Medical Chemistry and Biophysics, University of Umeå, SE-901 87 Umeå, Sweden.
- 700 1_
- $a Šachl, Radek $u J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v. v. i., Dolejškova 3, 182 23 Prague 8, Czech Republic. $7 xx0210158
- 700 1_
- $a Hof, Martin $u J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v. v. i., Dolejškova 3, 182 23 Prague 8, Czech Republic.
- 700 1_
- $a Gröbner, Gerhard $u Department of Chemistry, University of Umeå, SE-901 87 Umeå, Sweden. Electronic address: gerhard.grobner@chem.umu.se.
- 773 0_
- $w MED00009314 $t Biochimica et biophysica acta $x 0006-3002 $g Roč. 1858, č. 6 (2016), s. 1288-97
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/26947183 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20161005 $b ABA008
- 991 __
- $a 20170124161557 $b ABA008
- 999 __
- $a ok $b bmc $g 1165920 $s 952236
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2016 $b 1858 $c 6 $d 1288-97 $e 20160304 $i 0006-3002 $m Biochimica et biophysica acta $n Biochim Biophys Acta $x MED00009314
- LZP __
- $a Pubmed-20161005
