Apoptotic Bax at Oxidatively Stressed Mitochondrial Membranes: Lipid Dynamics and Permeabilization
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F17%3A00474912" target="_blank" >RIV/61388955:_____/17:00474912 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.bpj.2017.04.019" target="_blank" >http://dx.doi.org/10.1016/j.bpj.2017.04.019</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bpj.2017.04.019" target="_blank" >10.1016/j.bpj.2017.04.019</a>
Alternative languages
Result language
angličtina
Original language name
Apoptotic Bax at Oxidatively Stressed Mitochondrial Membranes: Lipid Dynamics and Permeabilization
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
<a href="/en/project/GBP208%2F12%2FG016" target="_blank" >GBP208/12/G016: Controlling structure and function of biomolecules at the molecular scale: theory meets experiment</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biophysical Journal
ISSN
0006-3495
e-ISSN
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Volume of the periodical
112
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
2147-2158
UT code for WoS article
000402119300015
EID of the result in the Scopus database
2-s2.0-85019768687