Cholesterol sensing, trafficking, and esterification.
Mammalian cells acquire cholesterol from low-density lipoprotein (LDL) and from endogenous biosynthesis. The roles of the Niemann-Pick type C1 protein in mediating the endosomal transport of LDL-derived cholesterol and endogenously synthesized cholesterol are discussed. Excess cellular cholesterol is converted to cholesteryl esters by the enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT) 1 or is removed from a cell by cellular cholesterol efflux at the plasma membrane. A close relationship between the ACAT substrate pool and the cholesterol efflux pool is proposed. Sterol-sensing domains (SSDs) are present in several membrane proteins, including NPC1, HMG-CoA reductase, and the SREBP cleavage-activating protein. The functions of SSDs are described. ACAT1 is an endoplasmic reticulum cholesterol sensor and contains a signature motif characteristic of the membrane-bound acyltransferase family. The nonvesicular cholesterol translocation processes involve the START domain proteins and the oxysterol binding protein-related proteins (ORPs). The properties of these proteins are summarized.
Chang
Ta-Yuan
TY
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA. ta.yuan.chang@dartmouth.edu
Chang
Catherine C Y
CC
Ohgami
Nobutaka
N
Yamauchi
Yoshio
Y
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D004951:Esterification; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D011284:Pregnenolone / Q000096:biosynthesis
D008562:Membrane Glycoproteins; D011284:Pregnenolone; D002784:Cholesterol