Steroidogenic acute regulatory protein (StAR) is a sterol transfer protein

J Biol Chem. 1998 Oct 9;273(41):26285-8. doi: 10.1074/jbc.273.41.26285.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Cattle
  • Cholesterol / metabolism
  • Humans
  • Membrane Proteins / metabolism*
  • Mice
  • Microsomes, Liver / metabolism
  • Phosphatidylcholines / metabolism
  • Phosphoproteins / metabolism*
  • Rats
  • Recombinant Proteins / metabolism

Substances

  • Membrane Proteins
  • Phosphatidylcholines
  • Phosphoproteins
  • Recombinant Proteins
  • steroidogenic acute regulatory protein
  • Cholesterol