Mitochondrial membranes: model lipid compositions, curvature elastic properties and the puzzle of cardiolipin

Konar, Sukanya; Allolio, Christoph

doi:10.1016/j.bpj.2021.11.1867

Cited by 2 publications

(3 citation statements)

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“…From simulations of planar membranes, we computed J s , κ , and κ θ , where values for POPC and POPE were taken from recent studies. 64,65 Table 1 demonstrates large variations of J s in the range between −0.14 nm −1 for POPE, characterizing a cone-shaped lipid, 66 up to 0.23 nm −1 for POPG, characterizing an highly inverted-cone-shaped lipid. As expected, the addition of lyso-16:0-PC or oleic acid to POPC imposes positive or negative J s , respectively, whereas the effect of cholesterol is hardly detectable within our statistical errors.…”

Section: Resultsmentioning

confidence: 99%

“…78 Continuum properties, i.e., spontaneous curvature, bending modulus, and tilt modulus were computed from equilibrium simulations of planar membranes as described previously. 64,65,79 Lipid director definitions as part of the lipidator-toolkit and a modified GROMACS version to calculate the local stress tensor are freely available at https://github.com/allolio. Additional computational details are described in the Supplementary Information, which contains the additional Refs.…”

Section: Methods Summarymentioning

confidence: 99%

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Pore formation in complex biological membranes: torn between evolutionary needs

Starke,

Allolio,

Hub

2024

Preprint

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The primary function of biological membranes is to enable compartmentalization among cells and organelles. Loss of integrity by the formation of membrane pores would trigger uncontrolled depolarization or influx of toxic compounds, posing a fatal thread to living cells. How the lipid complexity of biological membranes enables mechanical stability against pore formation while simultaneously allowing ongoing membrane remodeling is largely enigmatic. We performed molecular dynamics simulations of eight complex lipid membranes including the plasma membrane and membranes of the organelles ER, Golgi, lysosome, and mitochondrion. To quantify the mechanical stability of these membranes, we computed the free energies for nucleating a transmembrane pore as well as the line tension along the rim of open pores. Our simulations reveal that complex biological membranes are overall remarkably stable, however with the plasma membrane standing out as exceptionally stable, which aligns with its crucial role as a protective layer. We observe that sterol content is the main regulator for biomembrane stability, and that lateral sorting among lipid mixtures influences the energetics of membrane pores. A comparison of 25 model membranes with varying sterol content, tail length, tail saturation, and head group type shows that the pore nucleation free energy is mostly associated with the lipid tilt modulus, whereas the line tension along the pore rim is determined by the lipid intrinsic curvature. Together, our study provides an atomistic and energetic view on the role of lipid complexity on biomembrane stability.

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Section: Resultsmentioning

confidence: 99%

Section: Methods Summarymentioning

confidence: 99%

Pore formation in complex biological membranes: torn between evolutionary needs

Starke,

Allolio,

Hub

2024

Preprint

Self Cite

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“…To further compare the intrinsic properties of the two variants, a lipid vesicle permeabilization assay was used with large unilamellar vesicles (LUVs) composed of synthetic lipid vesicles mimicking the composition of the outer mitochondrial membrane (OMM) [57]. The two PB1-F2 variants were incubated with LUVs containing a fluorescent soluble probe (ANTS) and its quencher (DPX).…”

Section: Functional Characterization Of Equine Pb1-f2mentioning

confidence: 99%

Genome sequences of equine influenza A subtype H3N8 viruses by long read sequencing and functional characterization of the PB1-F2 virulence factor of A/equine/Paris/1/2018

Kleij,

Bruder,

Raoux-Barbot

et al. 2023

Preprint

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Equine influenza virus (EIV) remains a persistent threat to equines, despite the availability of vaccines. Currently, strategies to monitor the virus and prevent any potential vaccine failure revolve around serological assays, RT‒qPCR amplification, and sequencing the viral hemagglutinin (HA) and neuraminidase (NA) genes. These approaches overlook the contribution of other viral proteins in driving virulence. This study assesses the potential of long-read nanopore sequencing for swift and precise sequencing of circulating equine influenza viruses. To this end, two French Florida Clade 1 strains, including the one circulating in winter 2018-2019 exhibiting more pronounced pathogenicity than usual, as well as the two currently used OIE-recommended vaccine strains, were sequenced. Our results demonstrated the reliability of this sequencing method in generating accurate sequences. Sequence analysis of HA revealed a subtle antigenic drift in the French EIV strains, with specific substitutions, such as T163I in A/equine/Paris/1/2018 and the N188T mutation in post-2015 strains; both substitutions were located in antigenic site B. Antigenic site E exhibited modifications in post-2018 strains, with the N63D substitution. Segment 2 sequencing also revealed that the A/equine/Paris/1/2018 strain encodes a longer variant of the PB1-F2 protein when compared to other Florida clade 1 strains (90 amino acids long versus 81 amino acids long). Further biological and biochemistry assays demonstrated that this PB1-F2 variant has enhanced abilities to abolish the mitochondrial membrane electric potential and permeabilize synthetic membranes. Altogether, our results highlight the interest in rapidly characterizing the complete genome of circulating strains with next-generation sequencing technologies to adapt vaccines and identify specific virulence markers of EIV.

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Mitochondrial membranes: model lipid compositions, curvature elastic properties and the puzzle of cardiolipin

Cited by 2 publications

References 0 publications

Pore formation in complex biological membranes: torn between evolutionary needs

Pore formation in complex biological membranes: torn between evolutionary needs

Genome sequences of equine influenza A subtype H3N8 viruses by long read sequencing and functional characterization of the PB1-F2 virulence factor of A/equine/Paris/1/2018

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