The sterol regulatory element-binding protein pathway: control of lipid homeostasis through regulated intracellular...

The sterol regulatory element-binding proteins (SREBPs) are membrane-bound transcription factors that play a central role in cellular lipid homeostasis through the end-product feedback regulation of lipid synthesis. This feedback pathway is best understood in the case of cholesterol. Accumulation of cholesterol suppresses the proteolytic release of the transcriptionally active amino-terminal fragment of SREBP from the membrane-bound precursor. Experiments reported during the past year have led to a more complete understanding of the mechanisms that regulate the processing of SREBPs and their role in cellular lipid homeostasis. Regulation of lipid homeostasis is intimately associated with intracellular membrane trafficking; SREBPs undergo regulated transport from the endoplasmic reticulum to the Golgi apparatus in response to cellular lipid demand. The regulated step in this transport is the budding of a complex of SREBP and SREBP cleavage-activating protein into vesicles. In the present review we focus on recent results that give a more detailed picture of the mechanisms that are involved in end-product feedback regulation of lipid homeostasis.