Cholesterol transport in steroid biosynthesis: Role of protein-protein interactions and implications in disease states

Pathway 1: Cholesterol synthesized in the ER is trafficked to the Golgi apparatus where it can be targeted to the mitochondria via the PAP7 protein for steroidogenesis. Passive diffusion from the ER to the mitochondria, shown here with the corresponding cholesterol molecules present on both organelles, is another possible pathway for steroidogenic cholesterol to be transferred to the mitochondria. Pathway 2: Low density lipoprotein (LDL), containing cholesterol, binds to the LDL receptor and is trafficked through the endosomal pathway. MLN-64 assists with the transfer of cholesterol to the mitochondria from the late endosomes and lysosomes for use in steroidogenesis. NPC1 and NPC2 associate with MLN-64 for cholesterol transfer out of the lysosomes, although it is not known if this cholesterol is used for steroidogenesis. Pathway 3: Cholesterol is transferred from high density lipoprotein (HDL) to the plasma membrane by the SR-BI receptor. Hormone-sensitive lipase (HSL) converts esterified cholesterol from the plasma membrane to free cholesterol, which can be used for steroidogenesis. Pathway 4: HSL also interacts with esterified cholesterol present in the lipid droplets (LD), which converts esterified cholesterol to free cholesterol for use in steroidogenesis as well. Free cholesterol from the LD can interact with lipid-binding proteins present in the cytosol for delivery to the mitochondria.

Publication

Cholesterol transport in steroid biosynthesis: Role of protein-protein interactions and implications in disease states. () Malena B. Rone, et al. Biochim Biophys Acta. ;1791(7):646-658. Figure: F1. All organisms Homo sapiens Arabidopsis thaliana

Disease mentions