Abstract
Phospholipid membranes form cellular barriers but need to be flexible enough to divide by fission. Phospholipids generally contain a saturated fatty acid (FA) at position sn1 whereas the sn2-FA is saturated, monounsaturated or polyunsaturated. Our understanding of the impact of phospholipid unsaturation on membrane flexibility and fission is fragmentary. Here, we provide a comprehensive view of the effects of the FA profile of phospholipids on membrane vesiculation by dynamin and endophilin. Coupled to simulations, this analysis indicates that: (i) phospholipids with two polyunsaturated FAs make membranes prone to vesiculation but highly permeable; (ii) asymmetric sn1-saturated-sn2-polyunsaturated phospholipids provide a tradeoff between efficient membrane vesiculation and low membrane permeability; (iii) When incorporated into phospholipids, docosahexaenoic acid (DHA; omega-3) makes membranes more deformable than arachidonic acid (omega-6). These results suggest an explanation for the abundance of sn1-saturated-sn2-DHA phospholipids in synaptic membranes and for the importance of the omega-6/omega-3 ratio on neuronal functions.
Highlights
It is common knowledge that polyunsaturated fatty acids (PUFAs) especially omega-3 FAs are important for health, the underlying mechanisms are not fully understood (Bazinet and Laye, 2014; Marszalek and Lodish, 2005; Stillwell and Wassall, 2003)
We previously showed that phospholipids with the sn2 PUFA docosahexaenoic acid (DHA) facilitate the membrane shaping and fission activities of dynamin and endophilin (Pinot et al, 2014)
This second round of analysis is important because conditions exist where dynamin readily self-assembles and undergoes fast GTP hydrolysis and yet does not efficiently promote membrane vesiculation (Neumann and Schmid, 2013; Stowell et al, 1999)
Summary
It is common knowledge that polyunsaturated fatty acids (PUFAs) especially omega-3 FAs are important for health, the underlying mechanisms are not fully understood (Bazinet and Laye, 2014; Marszalek and Lodish, 2005; Stillwell and Wassall, 2003). The investigation showed that phospholipids with both saturated and unsaturated fatty acids strike a balance between impermeable and flexible membranes. The experiments revealed that omega-3 unsaturated fats aid flexibility more than omega-6 This finding may help to explain why the relative amounts of omega-3 and -6 are so important in the membranes of brain cells. Retinal discs show very high concentrations of phospholipids containing PUFAs (BoeszeBattaglia and Schimmel, 1997; Rice et al, 2015) These striking enrichments suggest that the fatty acyl chain profile of phospholipids could impact on the properties of cellular membranes. We previously showed that phospholipids with the sn PUFA DHA facilitate the membrane shaping and fission activities of dynamin and endophilin (Pinot et al, 2014).
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