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Examining the Effect of Charged Lipids on Mitochondrial Outer Membrane Dynamics Using Atomistic Simulations

The outer mitochondrial membrane (OMM) is involved in multiple cellular functions such as apoptosis, inflammation and signaling via its membrane-associated and -embedded proteins. Despite the central role of the OMM in these vital phenomena, the structure and dynamics of the membrane have regularly...

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Autores principales: Oliveira, Aline A., Róg, Tomasz, da Silva, Albérico B. F., Amaro, Rommie E., Johnson, Mark S., Postila, Pekka A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961577/
https://www.ncbi.nlm.nih.gov/pubmed/35204684
http://dx.doi.org/10.3390/biom12020183
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author Oliveira, Aline A.
Róg, Tomasz
da Silva, Albérico B. F.
Amaro, Rommie E.
Johnson, Mark S.
Postila, Pekka A.
author_facet Oliveira, Aline A.
Róg, Tomasz
da Silva, Albérico B. F.
Amaro, Rommie E.
Johnson, Mark S.
Postila, Pekka A.
author_sort Oliveira, Aline A.
collection PubMed
description The outer mitochondrial membrane (OMM) is involved in multiple cellular functions such as apoptosis, inflammation and signaling via its membrane-associated and -embedded proteins. Despite the central role of the OMM in these vital phenomena, the structure and dynamics of the membrane have regularly been investigated in silico using simple two-component models. Accordingly, the aim was to generate the realistic multi-component model of the OMM and inspect its properties using atomistic molecular dynamics (MD) simulations. All major lipid components, phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS), were included in the probed OMM models. Because increased levels of anionic PS lipids have potential effects on schizophrenia and, more specifically, on monoamine oxidase B enzyme activity, the effect of varying the PS concentration was explored. The MD simulations indicate that the complex membrane lipid composition (MLC) behavior is notably different from the two-component PC-PE model. The MLC changes caused relatively minor effects on the membrane structural properties such as membrane thickness or area per lipid; however, notable effects could be seen with the dynamical parameters at the water-membrane interface. Increase of PS levels appears to slow down lateral diffusion of all lipids and, in general, the presence of anionic lipids reduced hydration and slowed down the PE headgroup rotation. In addition, sodium ions could neutralize the membrane surface, when PI was the main anionic component; however, a similar effect was not seen for high PS levels. Based on these results, it is advisable for future studies on the OMM and its protein or ligand partners, especially when wanting to replicate the correct properties on the water-membrane interface, to use models that are sufficiently complex, containing anionic lipid types, PI in particular.
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spelling pubmed-89615772022-03-30 Examining the Effect of Charged Lipids on Mitochondrial Outer Membrane Dynamics Using Atomistic Simulations Oliveira, Aline A. Róg, Tomasz da Silva, Albérico B. F. Amaro, Rommie E. Johnson, Mark S. Postila, Pekka A. Biomolecules Article The outer mitochondrial membrane (OMM) is involved in multiple cellular functions such as apoptosis, inflammation and signaling via its membrane-associated and -embedded proteins. Despite the central role of the OMM in these vital phenomena, the structure and dynamics of the membrane have regularly been investigated in silico using simple two-component models. Accordingly, the aim was to generate the realistic multi-component model of the OMM and inspect its properties using atomistic molecular dynamics (MD) simulations. All major lipid components, phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS), were included in the probed OMM models. Because increased levels of anionic PS lipids have potential effects on schizophrenia and, more specifically, on monoamine oxidase B enzyme activity, the effect of varying the PS concentration was explored. The MD simulations indicate that the complex membrane lipid composition (MLC) behavior is notably different from the two-component PC-PE model. The MLC changes caused relatively minor effects on the membrane structural properties such as membrane thickness or area per lipid; however, notable effects could be seen with the dynamical parameters at the water-membrane interface. Increase of PS levels appears to slow down lateral diffusion of all lipids and, in general, the presence of anionic lipids reduced hydration and slowed down the PE headgroup rotation. In addition, sodium ions could neutralize the membrane surface, when PI was the main anionic component; however, a similar effect was not seen for high PS levels. Based on these results, it is advisable for future studies on the OMM and its protein or ligand partners, especially when wanting to replicate the correct properties on the water-membrane interface, to use models that are sufficiently complex, containing anionic lipid types, PI in particular. MDPI 2022-01-22 /pmc/articles/PMC8961577/ /pubmed/35204684 http://dx.doi.org/10.3390/biom12020183 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Oliveira, Aline A.
Róg, Tomasz
da Silva, Albérico B. F.
Amaro, Rommie E.
Johnson, Mark S.
Postila, Pekka A.
Examining the Effect of Charged Lipids on Mitochondrial Outer Membrane Dynamics Using Atomistic Simulations
title Examining the Effect of Charged Lipids on Mitochondrial Outer Membrane Dynamics Using Atomistic Simulations
title_full Examining the Effect of Charged Lipids on Mitochondrial Outer Membrane Dynamics Using Atomistic Simulations
title_fullStr Examining the Effect of Charged Lipids on Mitochondrial Outer Membrane Dynamics Using Atomistic Simulations
title_full_unstemmed Examining the Effect of Charged Lipids on Mitochondrial Outer Membrane Dynamics Using Atomistic Simulations
title_short Examining the Effect of Charged Lipids on Mitochondrial Outer Membrane Dynamics Using Atomistic Simulations
title_sort examining the effect of charged lipids on mitochondrial outer membrane dynamics using atomistic simulations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961577/
https://www.ncbi.nlm.nih.gov/pubmed/35204684
http://dx.doi.org/10.3390/biom12020183
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