StarD4-mediated translocation of 7-hydroperoxycholesterol to isolated mitochondria: deleterious effects and implications for steroidogenesis under oxidative stress conditions. Biochem Biophys Res Commun 2010 Jan 29;392(1):58-62
Date
01/12/2010Pubmed ID
20059974Pubmed Central ID
PMC2829839DOI
10.1016/j.bbrc.2009.12.165Scopus ID
2-s2.0-74849110791 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
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.
Author List
Korytowski W, Rodriguez-Agudo D, Pilat A, Girotti AWAuthor
Albert W. Girotti PhD Adjunct Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBiological Transport
Cell Fractionation
Cholesterol
Humans
Lipid Peroxidation
Membrane Potential, Mitochondrial
Membrane Transport Proteins
Mice
Mitochondria, Liver
Oxidative Stress
Recombinant Proteins
