Do sterols reduce proton and sodium leaks through lipid bilayers?

Haines, Thomas H.

doi:10.1016/s0163-7827(01)00009-1

Cited by 348 publications

(280 citation statements)

References 110 publications

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“…Instead, we demonstrate through in vitro experiments with protein-free artificial liposomes and through in vivo morphotyping that Q8 enhances membrane stability, strongly suggesting a causal link between Q8 accumulation and osmotic stress resistance by direct stabilization of the cytoplasmic membrane. Because Q8 accumulated to up to 1% of main membrane lipids in vivo whereas liposome stabilization required at least 5% Q10 content, we cannot exclude that Q8 accumulation might additionally improve function or stability of membrane proteins by direct interactions with their membrane-localized domains 37 or by molecular crowding 14,38 , or alter bioenergetic membrane properties by reducing sodium ion leakage 39 .…”

Section: Discussionmentioning

confidence: 99%

“…Upon exposure to conditions of osmotic stress and apparently independent of transcriptional regulation, a yet unknown regulatory mechanism triggers the accumulation of Q8 to up to 1% of total membrane lipids. The Q8 molecule has been shown to reside flat in the center of the lipid bilayer 32,39 , implying that the observed substantial accumulation of Q8 would increase the hydrophobic thickness of the cytoplasmic membrane. Intriguingly, such an effect has already been observed in vitro with the isoprenoid zeaxanthin, of which concentrations between 1% and 10% increased the hydrophobic thickness of artificial lipid bilayer membranes 40 .…”

Section: Discussionmentioning

confidence: 99%

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Ubiquinone accumulation improves osmotic-stress tolerance in Escherichia coli

2014

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Bacteria are thought to cope with fluctuating environmental solute concentrations primarily by adjusting the osmolality of their cytoplasm. To obtain insights into underlying metabolic adaptions, we analyzed the global metabolic response of Escherichia coli to sustained hyperosmotic stress using non-targeted mass spectrometry. We observed that 52% of 1,071 detected metabolites, including known osmoprotectants, changed abundance with increasing salt challenge. Unexpectedly, unsupervised data analysis revealed a substantial increase of most intermediates in the ubiquinone-8 (Q8) biosynthesis pathway and a 110-fold accumulation of Q8 itself, as confirmed by quantitative lipidomics. We then demonstrate that Q8 is necessary for acute and sustained osmotic stress tolerance using Q8 mutants and tolerance rescue through feeding non-respiratory Q8 analogues. Finally, in vitro experiments with artificial liposomes reveal mechanical membrane stabilization as a principal mechanism of Q8-mediated osmoprotection. Thus, we find that besides regulating intracellular osmolality, E. coli enhances its cytoplasmic membrane stability to withstand osmotic stress. AbstractBacteria are thought to cope with fluctuating environmental solute concentrations primarily by adjusting the osmolality of their cytoplasm. To obtain insights into underlying metabolic adaptions, we analyzed the global metabolic response of Escherichia coli to sustained hyperosmotic stress using non-targeted mass spectrometry. We observed that 52% of 1,071 detected metabolites, including known osmoprotectants, changed abundance with increasing salt challenge. Unexpectedly, unsupervised data analysis revealed a substantial increase of most intermediates in the ubiquinone-8 (Q8) biosynthesis pathway and a 110-fold accumulation of Q8 itself, as confirmed by quantitative lipidomics. We then demonstrate that Q8 is necessary for acute and sustained osmotic stress tolerance using Q8 mutants and tolerance rescue through feeding non-respiratory Q8 analogues.Finally, in vitro experiments with artificial liposomes reveal mechanical membrane stabilization as a principal mechanism of Q8-mediated osmoprotection. Thus, we find that besides regulating intracellular osmolality, E. coli enhances its cytoplasmic membrane stability to withstand osmotic stress.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ubiquinone accumulation improves osmotic-stress tolerance in Escherichia coli

2014

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“…These include decreased cholesterol production leading to cholesterol depletion in the myocyte membranes (Harper and Jacobson 2007), and blocked HMG-CoA reductase activity resulting in decreased prenylation and thus altered function of small GTP-ases (Wang et al 2007). Normal cholesterol levels in phospholipids bilayers seem important in reducing Na + leakage through these membranes and, therefore, lowering the energy expenditure of the Na + -K + -pump and thus preventing ATP depletion of the cell (Haines 2001). Reduced amounts of cholesterol in the surface membrane would then lead to ATP depletion and, therefore, altered calcium homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Fluvastatin-induced alterations of skeletal muscle function in hypercholesterolaemic rats

Füzi

Palicz

Vincze

et al. 2011

J Muscle Res Cell Motil

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Although statins, the most widely used drugs in the treatment of hyperlipidaemia, are generally accepted as efficient and safe drugs their side-effects on skeletal muscle have been reported with increasing frequency in the past years. The lack of an appropriate animal model in which these side effects would consistently be observed is one of the most important drawbacks in studying statin associated myopathy. To overcome this and enable the studying of the effects of fluvastatin on skeletal muscles an animal model with high blood cholesterol levels was developed. In these animals cholesterol levels rose more than seven fold (from soleus the duration of twitch and tetanic force was shortened. These results clearly indicate that statin administration in these animals results in a myopathy characterized by decreased muscle force and elevated plasma creatine kinase level.

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“…Interestingly, hydroxyl and amino groups are located at the end of the short aliphatic chain, providing some kind of "inverted" polarity on comparing to other sterols. They occur almost exclusively in membranes which contain large proton gradients [25]. It has been proposed that they have a role in inhibiting proton leaks through membranes and would reinforce membrane cohesion in bacteria as do eukaryotic sterols [2].…”

Section: Effect Of Hopanoids On Model Membranesmentioning

confidence: 99%

Sterols and membrane dynamics

2008

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The effect of sterols from mammals, plants, fungi, and bacteria on model and natural membrane dynamics are reviewed, in the frame of ordering-disordering properties of membranes. It is shown that all sterols share a common property: the ability to regulate dynamics in order to maintain membranes in a microfluid state where it can convey important biological processes. Depending on the sterol class, this property is modulated by molecular modifications that have occurred during evolution. The role of sterols in rafts, antibiotic complexes, and in protecting membranes from the destructive action of amphipathic toxins is also discussed.

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Do sterols reduce proton and sodium leaks through lipid bilayers?

Cited by 348 publications

References 110 publications

Ubiquinone accumulation improves osmotic-stress tolerance in Escherichia coli

Ubiquinone accumulation improves osmotic-stress tolerance in Escherichia coli

Fluvastatin-induced alterations of skeletal muscle function in hypercholesterolaemic rats

Sterols and membrane dynamics

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