Tom40参与胆固醇转运。
Tom40 in cholesterol transport.
作者信息
Bose Himangshu S, Bose Mahuya, Whittal Randy M
机构信息
Laboratory of Biochemistry and Cell Biology, Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA.
Anderson Cancer Institute, Memorial University Medical Center, Savannah, GA 31404, USA.
出版信息
iScience. 2023 Mar 11;26(4):106386. doi: 10.1016/j.isci.2023.106386. eCollection 2023 Apr 21.
Cholesterol initiates steroid metabolism in adrenal and gonadal mitochondria, which is essential for all mammalian survival. During stress an increased cholesterol transport rapidly increases steroidogenesis; however, the mechanism of mitochondrial cholesterol transport is unknown. Using rat testicular tissue and mouse Leydig (MA-10) cells, we report for the first time that mitochondrial translocase of outer mitochondrial membrane (OMM), Tom40, is central in cholesterol transport. Cytoplasmic cholesterol-lipids complex containing StAR protein move from the mitochondria-associated ER membrane (MAM) to the OMM, increasing cholesterol load. Tom40 interacts with StAR at the OMM increasing cholesterol transport into mitochondria. An absence of Tom40 disassembles complex formation and inhibits mitochondrial cholesterol transport and steroidogenesis. Therefore, Tom40 is essential for rapid mitochondrial cholesterol transport to initiate, maintain, and regulate activity.
胆固醇启动肾上腺和性腺线粒体中的类固醇代谢，这对所有哺乳动物的生存至关重要。在应激期间，胆固醇转运增加会迅速促进类固醇生成；然而，线粒体胆固醇转运的机制尚不清楚。利用大鼠睾丸组织和小鼠睾丸间质（MA-10）细胞，我们首次报道线粒体外膜转位酶（OMM）Tom40在胆固醇转运中起核心作用。含有类固醇生成急性调节蛋白（StAR）的细胞质胆固醇-脂质复合物从线粒体相关内质网膜（MAM）移动到线粒体外膜，增加胆固醇负载。Tom40在线粒体外膜与StAR相互作用，增加胆固醇向线粒体的转运。Tom40的缺失会破坏复合物的形成，并抑制线粒体胆固醇转运和类固醇生成。因此，Tom40对于启动、维持和调节线粒体快速胆固醇转运的活性至关重要。
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