Membrane contact site
[1] These sites are thought to be important to facilitate signalling, and they promote the passage of small molecules, including ions, lipids[2] and (discovered later) reactive oxygen species.Some studies showed that more than 1000 contact sites are present in every yeast cell and the distance between the lipid bilayer ranges from 10 to 25 nm (the order of the size of a single protein).In yeast, Osh4 is an OSBP homologue the crystal structure of which, obtained in both the sterol-bound and unbound states, showed a soluble β-barrel protein with a hydrophilic external surface and a hydrophobic pocket that can carry a single sterol molecule.They localize to the ER, and their ability to interact with multiple lipid-transfer, lipid-binding or lipid-sensing proteins containing the FFAT motif, suggests that VAPs have a role in lipid transport at the MCSs.In these contact sites, voltage-gated Ca2+ channels (VGCCs) activate closely apposed ryanodine receptors expressed on the ER to trigger calcium release during excitation-contraction coupling.In the "MAM hypothesis" it has been proposed that at the centre of the pathogenesis of Alzheimer's disease resides the disorder of ER-mitochondrial contact sites rather than Amyloid plaques or Neurofibrillary tangles.Furthermore, they suggested the existence of a regulatory feedback mechanism that limits the accumulation of cardiolipin in mitochondria: high cardiolipin concentrations have the final results to inhibit its synthesis and the mitochondrial import of PA.[20] Another study by Lahiri et al. has demonstrated that loss of contacts between the ER and mitochondria results in severe reduction in mitochondrial biosynthesis of phosphatidylethanolamine (PE) due to reduction in transport of phosphatidylserine (PS), which is the precursor for PE synthesis.