Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90089, USA.
Endocrinology. 2022 Aug 1;163(8). doi: 10.1210/endocr/bqac091.
The steroidogenic acute regulatory protein (STAR; STARD1) is critical for the transport of cholesterol into the mitochondria for hormone-induced steroidogenesis. Steroidogenic cells express STAR under control conditions (constitutive STAR). On hormonal stimulation, STAR localizes to the outer mitochondrial membrane (OMM) where it facilitates cholesterol transport and where it is processed to its mature form. Here, we show that knockout of Star in MA-10 mouse tumor Leydig cells (STARKO1) causes defects in mitochondrial structure and function under basal conditions. We also show that overexpression of Star in STARKO1 cells exacerbates, rather than recovers, mitochondrial structure and function, which further disrupts the processing of STAR at the OMM. Our findings suggest that constitutive STAR is necessary for proper mitochondrial structure and function and that mitochondrial dysfunction leads to defective STAR processing at the OMM.
类固醇生成急性调节蛋白（STAR；STARD1）对于胆固醇向线粒体的转运至关重要，以便进行激素诱导的类固醇生成。在控制条件下，类固醇生成细胞表达 STAR（组成性 STAR）。在激素刺激下，STAR 定位于外线粒体膜（OMM），在那里它促进胆固醇的转运，并在此被加工成成熟形式。在这里，我们表明，在 MA-10 小鼠肿瘤睾丸间质细胞瘤（STARKO1）中敲除 Star 会导致基础条件下线粒体结构和功能的缺陷。我们还表明，在 STARKO1 细胞中过表达 Star 会加剧而不是恢复线粒体的结构和功能，这进一步破坏了 OMM 处 STAR 的加工。我们的发现表明，组成性 STAR 对于正常的线粒体结构和功能是必要的，并且线粒体功能障碍导致 OMM 处的 STAR 加工缺陷。
