The asymmetric combination of saturated and polyunsaturated acyl chains in phospholipids as typically observed in synapses makes membranes prone to deformation and fission without compromising their impermeability.
Inhibition of C. elegans FLD-1 or Human TLCD1/2 prevents saturated fat lipotoxicity by allowing increased levels of membrane phospholipids that contain fluidizing long-chain polyunsaturated fatty acids.
Silencing the acyl-coA synthethase ACSL1 protects against saturated fat lipotoxicity by preventing the degradation of polyunsaturated fatty acids, allowing them to be incorporated into phospholipids and improves membrane fluidity.
The C2-domain of cytoplasmic phospholipase A2α is structurally designed to target PC-rich membrane regions to increase the enzymatic efficiency of the catalytic domain, which prefers PCs with polyunsaturated acyl chains.
The RNA-binding protein MSI1, which is required for stem cell and cancer cell proliferation in the brain and epithelial tissues, also directly senses the concentration of long non-esterified omega-9 fatty acids.