Intracellular trafficking of vitamin E by the α‐tocopherol transfer protein

Abstract

Vitamin E, a plant-derived neutral lipid, is an essential nutrient for all vertebrates that scavenges free radicals in biological membranes, thereby preventing oxidative stress. Of the eight naturally-occurring forms of vitamin E, α-tocopherol is the most biologically active. This discrimination is achieved by the selective retention of α-tocopherol by the hepatic α-tocopherol transfer protein (α-TTP), and by the selective degradation of other vitamin E isoforms by hepatic cytochrome P450. In hepatocytes, α-TTP facilitates the secretion of α-tocopherol to circulating lipoproteins for uptake by extrahepatic tissues. We aim to understand the molecular mechanisms that regulate α-TTP in vivo. Using live-cell fluorescence imaging, we found that the intracellular localization of α-TTP in hepatocytes is dynamic: in the absence of α-tocopherol, the protein is found in a punctate perinuclear pattern, but upon addition of vitamin E, the protein redistributes to a diffuse cytosolic pattern. The vitamin E-induced change in α-TTP localization is time- and dose-dependent. This change in localization may be an indication that α-TTP is a direct carrier of vitamin E that shuttles α-tocopherol between distinct cytosolic locations.