Lim Jung Mi
Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
Contact (Thousand Oaks). 2024 Jan 2;7:25152564231223480. doi: 10.1177/25152564231223480. eCollection 2024 Jan-Dec.
In this News and Views, I discuss our recent publication that established how steroidogenic acute regulatory-related lipid transfer domain-3 (STARD3), a membrane contact protein situated at lysosomal membranes, plays a role in the detoxification of cholesterol hydroperoxide. STARD3's methionine residues can be oxidized to methionine sulfoxide by cholesterol hydroperoxide, after which methionine sulfoxide reductases reduce the methionine sulfoxide residues back to methionine. The reaction also results in the reduction of the cholesterol hydroperoxide to an alcohol. The cyclic oxidation and reduction of methionine residues in STARD3 at membrane contact sites creates a catalytically efficient mechanism for detoxification of cholesterol hydroperoxide during cholesterol transport, thus protecting membrane contact sites and the entire cell against the toxicity of cholesterol hydroperoxide.
在这篇“新闻与观点”文章中，我将讨论我们最近发表的研究成果，该研究确定了位于溶酶体膜上的膜接触蛋白——类固醇生成急性调节相关脂质转移结构域3（STARD3）在胆固醇氢过氧化物解毒过程中所起的作用。STARD3的甲硫氨酸残基可被胆固醇氢过氧化物氧化为甲硫氨酸亚砜，之后甲硫氨酸亚砜还原酶将甲硫氨酸亚砜残基还原回甲硫氨酸。该反应还会使胆固醇氢过氧化物还原为醇。在膜接触位点，STARD3中甲硫氨酸残基的循环氧化和还原为胆固醇运输过程中胆固醇氢过氧化物的解毒创造了一种催化效率高的机制，从而保护膜接触位点和整个细胞免受胆固醇氢过氧化物的毒性影响。
