Steroidogenic acute regulatory protein (StAR) is a sterol transfer protein.
Steroidogenic acute regulatory protein (StAR) plays a critical role in steroidogenesis by enhancing the delivery of substrate cholesterol from the outer mitochondrial membrane to the cholesterol side chain cleavage enzyme system on the inner membrane. A recombinant StAR protein lacking the first N-terminal 62 amino acid residues that includes the mitochondrial targeting sequence was shown to stimulate the transfer of cholesterol and beta-sitosterol from liposomes to heat-treated mitochondria in a dose-, time-, and temperature-dependent manner. A recombinant mutant StAR protein that cannot stimulate steroidogenesis by isolated mitochondria did not promote sterol transfer. Unlike the more promiscuous lipid transfer protein, sterol carrier protein 2 (SCP2), StAR did not stimulate phosphatidylcholine transfer in our assay system. The recombinant StAR protein increased cholesterol transfer to heat-treated microsomes as well as to heat- and trypsin-treated mitochondria. These observations demonstrate that StAR has sterol transfer activity, which may reflect an ability to enhance desorption of cholesterol from sterol-rich donor membranes. We suggest that the ability of StAR to promote sterol transfer explains its steroidogenic activity.
Kallen
C B
CB
Center for Research on Reproduction and Women's Health, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
Billheimer
J T
JT
Summers
S A
SA
Stayrook
S E
SE
Lewis
M
M
Strauss
J F
JF
D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
D008565:Membrane Proteins; D010713:Phosphatidylcholines; D010750:Phosphoproteins; D011994:Recombinant Proteins; D000098682:Steroidogenic Acute Regulatory Protein; D002784:Cholesterol