Basic mechanisms of cholesterol transport between two membranes. (a) Vesicular transport. This process requires ATP but does not require a change in the transversal distribution of cholesterol in the donor membrane. (b) Diffusion through the cytoplasm either bound to a carrier protein (upper arrows) or by free diffusion (lower arrows). Cholesterol in the donor membrane must desorb from the cytoplasmic leaflet, so the transbilayer distribution of cholesterol can affect this process. (c) Transport across membrane contacts. Adjacent donor and acceptor membranes come into close contact, resulting in cholesterol shuttling across the intermembrane space. This process requires cholesterol in the cytosolic leaflet of the donor membrane and may be facilitated by transport proteins.