Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Biochem Biophys Res Commun. 2010 Jan 29;392(1):58-62. doi: 10.1016/j.bbrc.2009.12.165. Epub 2010 Jan 6.
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.
StAR 家族蛋白，包括 StarD4，在类固醇生成中起着关键作用，通过将胆固醇（Ch）转运到线粒体中转化为孕烯醇酮。使用包含过氧化胆固醇（7α-OOH）的脂质体作为供体的模型系统，我们表明人重组 StarD4 加速了 7α-OOH 向分离的肝线粒体的转移，并且比 Ch 转移更有效。StarD4 对非氧化或过氧化磷脂酰胆碱的转移没有影响，这与甾醇环的特异性一致。StarD4 加速的 7α-OOH 向线粒体的转移导致对自由基脂质过氧化和膜电位丧失的敏感性增加，超过了非 StarD4 对照。这些发现的新含义是，在氧化应激状态下，类固醇生成组织中不当的 StAR 介导的过氧化 Ch 转运可能导致选择性靶向线粒体的损伤和功能障碍。
