Lipid Organization of the Plasma Membrane

Ingólfsson, Helgi I.; Tieleman, Peter; Marrink, Siewert J.

doi:10.1016/j.bpj.2014.11.1962

Cited by 47 publications

(61 citation statements)

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“…It is generally accepted that cellular membranes are asymmetric bimolecular leaflets composed predominantly of phospholipids, varying concentrations of cholesterol, other minor species of lipids, and a plethora of proteins (1,61,62). Because of its fast flip-flop rate, the cholesterol distribution across the two leaflets of the plasma membrane has been quite challenging to determine, with experiments suggesting either an outer or inner leaflet enrichment (23,63).…”

Section: Discussionmentioning

confidence: 99%

“…Because of its fast flip-flop rate, the cholesterol distribution across the two leaflets of the plasma membrane has been quite challenging to determine, with experiments suggesting either an outer or inner leaflet enrichment (23,63). A recent study, based on a large scale molecular dynamics simulation, showed an asymPlasma Membrane Cholesterol in Steroidogenesis DECEMBER 9, 2016 • VOLUME 291 • NUMBER 50 metrical distribution of cholesterol, in which the outer leaflet of the plasma membrane included 54% of the total cholesterol with a slightly higher cholesterol content than the inner leaflet (comprising 46%) (62).…”

Section: Discussionmentioning

confidence: 99%

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Plasma Membrane Origin of the Steroidogenic Pool of Cholesterol Used in Hormone-induced Acute Steroid Formation in Leydig Cells

Venugopal

Martinez–Arguelles

Chebbi

et al. 2016

Journal of Biological Chemistry

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Edited by George CarmanHormone-sensitive acute steroid biosynthesis requires trafficking of cholesterol from intracellular sources to the inner mitochondrial membrane. The precise location of the intracellular cholesterol and its transport mechanism are uncertain. Perfringolysin O, produced by Clostridium perfringens, binds cholesterol. Its fourth domain (D4) retains cholesterol-binding properties but not cytotoxicity. We transfected steroidogenic MA-10 cells of mouse Leydig cell tumors with the mCherry-D4 plasmid. Tagged D4 with fluorescent proteins enabled us to track cholesterol. The staining was primarily localized to the inner leaflet of the plasma membrane and was partially released upon treatment with dibutyryl-cAMP (Bt 2 cAMP), a cAMP analog. Inhibitors of cholesterol import into mitochondria blocked steroidogenesis and prevented release of D4 (and presumably cholesterol) from the plasma membrane. We conclude that the bulk of the steroidogenic pool of cholesterol, mobilized by Bt 2 cAMP for acute steroidogenesis, originates from the plasma membrane. Treatment of the cells with steroid metabolites, 22(R)-hydroxycholesterol and pregnenolone, also reduced D4 release from the plasma membrane, perhaps evidence for a feedback effect of elevated steroid formation on cholesterol release. Interestingly, D4 staining was localized to endosomes during Bt 2 cAMP stimulation suggesting that these organelles are on the route of cholesterol trafficking from the plasma membrane to mitochondria. Finally, D4 was expressed in primary rat Leydig cells with a lentivirus and was released from the plasma membrane following Bt 2 cAMP treatment. We conclude that the plasma membrane is the source of cholesterol for steroidogenesis in these cells as well as in MA-10 cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Plasma Membrane Origin of the Steroidogenic Pool of Cholesterol Used in Hormone-induced Acute Steroid Formation in Leydig Cells

Venugopal

Martinez–Arguelles

Chebbi

et al. 2016

Journal of Biological Chemistry

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“…Hydrocarbons May Induce Membrane Flexibility by Accumulating within the Lipid Bilayer Molecular dynamics simulations have become an invaluable technique used to investigate the nanoscale organization of lipid membranes (Marrink et al, 2009;Vattulainen and Rog, 2011), particularly in complex membrane systems (Ingólfsson et al, 2014;Manna et al, 2014). In order to understand how hydrocarbons could affect membrane properties, a novel symmetrical membrane model system was simulated based on the pseudoatomistic Martini force field, with an approximately 4:1 mapping of heavy atoms to coarse-grained particles (Supplemental Fig.…”

Section: The Absence Of Hydrocarbons Has Minor Effects On Photosynthementioning

confidence: 99%

Hydrocarbons Are Essential for Optimal Cell Size, Division, and Growth of Cyanobacteria

et al. 2016

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Cyanobacteria are intricately organized, incorporating an array of internal thylakoid membranes, the site of photosynthesis, into cells no larger than other bacteria. They also synthesize C15-C19 alkanes and alkenes, which results in substantial production of hydrocarbons in the environment. All sequenced cyanobacteria encode hydrocarbon biosynthesis pathways, suggesting an important, undefined physiological role for these compounds. Here, we demonstrate that hydrocarbon-deficient mutants of Synechococcus sp. PCC 7002 and Synechocystis sp. PCC 6803 exhibit significant phenotypic differences from wild type, including enlarged cell size, reduced growth, and increased division defects. Photosynthetic rates were similar between strains, although a minor reduction in energy transfer between the soluble light harvesting phycobilisome complex and membrane-bound photosystems was observed. Hydrocarbons were shown to accumulate in thylakoid and cytoplasmic membranes. Modeling of membranes suggests these compounds aggregate in the center of the lipid bilayer, potentially promoting membrane flexibility and facilitating curvature. In vivo measurements confirmed that Synechococcus sp. PCC 7002 mutants lacking hydrocarbons exhibit reduced thylakoid membrane curvature compared to wild type. We propose that hydrocarbons may have a role in inducing the flexibility in membranes required for optimal cell division, size, and growth, and efficient association of soluble and membrane bound proteins. The recent identification of C15-C17 alkanes and alkenes in microalgal species suggests hydrocarbons may serve a similar function in a broad range of photosynthetic organisms.

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“…E06 mAb binds several by-products of the oxidation of phosphatidylcholine, often referred to as Ox-PC (51). Because phosphatidylcholine is a major component of the outer leaflet of the plasma membrane, it seemed reasonable that this antibody might be sufficient to display an effect (52). Cells were pretreated with E06 mAb (50 g/ml) or a control IgM monoclonal antibody not targeting oxidized lipids (its epitope are advanced glycation end products) (41).…”

Section: Identification Of Efficient Cpps and Robustmentioning

confidence: 99%

Membrane Oxidation Enables the Cytosolic Entry of Polyarginine Cell-penetrating Peptides

Wang

Sun

Muthukrishnan

et al. 2016

Journal of Biological Chemistry

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Arginine-rich peptides can penetrate cells and consequently be used as delivery agents in various cellular applications. The activity of these reagents is often context-dependent, and the parameters that impact cell entry are not fully understood, giving rise to variability and limiting progress toward their usage. Herein, we report that the cytosolic penetration of linear polyarginine peptides is dependent on the oxidation state of the cell. In particular, we find that hypoxia and cellular antioxidants inhibit cell penetration. In contrast, oxidants promote cytosolic cell entry with an efficiency proportional to the level of reactive oxygen species generated within membranes. Moreover, an antibody that binds to oxidized lipids inhibits cell penetration, whereas extracellularly administered pure oxidized lipids enhance peptide transport into cells. Overall, these data indicate that oxidized lipids are capable of mediating the transport of polyarginine peptides across membranes. These data may also explain variability in cell-penetrating peptide performance in different experimental conditions. These new findings therefore provide new opportunities for the rational design of future cell-permeable compounds and for the optimization of delivery protocols.

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Lipid Organization of the Plasma Membrane

Cited by 47 publications

References 0 publications

Plasma Membrane Origin of the Steroidogenic Pool of Cholesterol Used in Hormone-induced Acute Steroid Formation in Leydig Cells

Plasma Membrane Origin of the Steroidogenic Pool of Cholesterol Used in Hormone-induced Acute Steroid Formation in Leydig Cells

Hydrocarbons Are Essential for Optimal Cell Size, Division, and Growth of Cyanobacteria

Membrane Oxidation Enables the Cytosolic Entry of Polyarginine Cell-penetrating Peptides

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