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Delivery of low-density lipoprotein from endocytic carriers to mitochondria supports steroidogenesis.

التفاصيل البيبلوغرافية
العنوان: Delivery of low-density lipoprotein from endocytic carriers to mitochondria supports steroidogenesis.
المؤلفون: Zhou YX; College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Taikang Center for Life and Medical Sciences, Taikang Medical School, Wuhan University, Wuhan, China., Wei J; College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Taikang Center for Life and Medical Sciences, Taikang Medical School, Wuhan University, Wuhan, China., Deng G; College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Taikang Center for Life and Medical Sciences, Taikang Medical School, Wuhan University, Wuhan, China., Hu A; College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Taikang Center for Life and Medical Sciences, Taikang Medical School, Wuhan University, Wuhan, China., Sun PY; College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Taikang Center for Life and Medical Sciences, Taikang Medical School, Wuhan University, Wuhan, China., Zhao X; College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Taikang Center for Life and Medical Sciences, Taikang Medical School, Wuhan University, Wuhan, China., Song BL; College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Taikang Center for Life and Medical Sciences, Taikang Medical School, Wuhan University, Wuhan, China. blsong@whu.edu.cn., Luo J; College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Taikang Center for Life and Medical Sciences, Taikang Medical School, Wuhan University, Wuhan, China. jieluo@whu.edu.cn.
المصدر: Nature cell biology [Nat Cell Biol] 2023 Jul; Vol. 25 (7), pp. 937-949. Date of Electronic Publication: 2023 Jun 05.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Macmillan Magazines Ltd Country of Publication: England NLM ID: 100890575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4679 (Electronic) Linking ISSN: 14657392 NLM ISO Abbreviation: Nat Cell Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Macmillan Magazines Ltd., [1999-
مواضيع طبية MeSH: Cholesterol*/metabolism , Mitochondria*/metabolism, Cholesterol, LDL ; Membrane Proteins/metabolism ; Hormones
مستخلص: The low-density lipoprotein (LDL) is a major cholesterol carrier in circulation and is internalized into cells through LDL receptor (LDLR)-mediated endocytosis. The LDLR protein is highly expressed in the steroidogenic organs and LDL cholesterol is an important source for steroidogenesis. Cholesterol must be transported into the mitochondria, where steroid hormone biosynthesis initiates. However, how LDL cholesterol is conveyed to the mitochondria is poorly defined. Here, through genome-wide small hairpin RNA screening, we find that the outer mitochondrial membrane protein phospholipase D6 (PLD6), which hydrolyses cardiolipin to phosphatidic acid, accelerates LDLR degradation. PLD6 promotes the entrance of LDL and LDLR into the mitochondria, where LDLR is degraded by mitochondrial proteases and LDL-carried cholesterol is used for steroid hormone biosynthesis. Mechanistically, the outer mitochondrial membrane protein CISD2 binds to the cytosolic tail of LDLR and tethers LDLR + vesicles to the mitochondria. The fusogenic lipid phosphatidic acid generated by PLD6 facilitates the membrane fusion of LDLR + vesicles with the mitochondria. This intracellular transport pathway of LDL-LDLR bypasses the lysosomes and delivers cholesterol to the mitochondria for steroidogenesis.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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معلومات مُعتمدة: 91954203 National Natural Science Foundation of China (National Science Foundation of China); 32021003 National Natural Science Foundation of China (National Science Foundation of China); 32293203 National Natural Science Foundation of China (National Science Foundation of China); 2018YFA0800703 Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)
المشرفين على المادة: 0 (Cholesterol, LDL)
97C5T2UQ7J (Cholesterol)
0 (Membrane Proteins)
0 (Hormones)
تواريخ الأحداث: Date Created: 20230605 Date Completed: 20230717 Latest Revision: 20231116
رمز التحديث: 20240628
DOI: 10.1038/s41556-023-01160-6
PMID: 37277481
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4679
DOI:10.1038/s41556-023-01160-6