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

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.