4.6 Article

StarD4-mediated translocation of 7-hydroperoxycholesterol to isolated mitochondria: Deleterious effects and implications for steroidogenesis under oxidative stress conditions

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.12.165

Keywords

Oxidative stress; Cholesterol hydroperoxide; StAR proteins; Lipid trafficking; Steroidogenesis

Funding

  1. NIH [CA72630, HL85677]
  2. Polish Ministry of Science [N301 08332/3232]
  3. American Heart Association

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StAR family proteins, including StarD4, play a key role in steroidogenesis by transporting cholesterol (Ch) into mitochondria for conversion to pregnenolone. Using a model system consisting of peroxidized cholesterol (7 alpha-OOH)-containing liposomes as donors, we showed that human recombinant StarD4 accelerates 7 alpha-OOH transfer to isolated liver mitochondria, and to a greater extent than Ch transfer. StarD4 had no effect on transfer of non-oxidized or peroxidized phosphatidylcholine, consistent with sterol ring specificity. StarD4-accelerated 7 alpha-OOH transfer to mitochondria resulted in greater susceptibility to free radical lipid peroxidation and loss of membrane potential than in a non-StarD4 control. The novel implication of these findings is that in oxidative stress states, inappropriate StAR-mediated trafficking of peroxidized Ch in steroidogenic tissues could result in damage and dysfunction selectively targeted to mitochondria. (C) 2010 Elsevier Inc. All rights reserved.

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