التفاصيل البيبلوغرافية
| العنوان: |
Defects in CYB5A and CYB5B impact sterol-C4 oxidation in cholesterol biosynthesis and demonstrate regulatory roles of dimethyl sterols |
| المؤلفون: |
Mei-Yan Ma, Gang Deng, Wen-Zhuo Zhu, Ming Sun, Lu-Yi Jiang, Wei-Hui Li, Yuan-Bin Liu, Lin Guo, Bao-Liang Song, Xiaolu Zhao |
| المصدر: |
Cell Reports, Vol 43, Iss 11, Pp 114912- (2024) |
| بيانات النشر: |
Elsevier, 2024. |
| سنة النشر: |
2024 |
| المجموعة: |
LCC:Biology (General) |
| مصطلحات موضوعية: |
CP: Metabolism, Biology (General), QH301-705.5 |
| الوصف: |
Summary: Cytochrome b5 (CYB5) is a hemoprotein crucial for electron transfer to oxygenases. Although microsomal CYB5A is required for sterol C4-demethylation in vitro, cholesterol biosynthesis remains intact in Cyb5a knockout mice. Here, we show that knockout of mitochondrial CYB5B, rather than CYB5A, blocks cholesterol biosynthesis at the sterol-C4 oxidation step in HeLa cells, causing an accumulation of testis meiosis-activating sterol (T-MAS) and dihydro-T-MAS. Surprisingly, liver-specific Cyb5b knockout (L-Cyb5b−/−) mice exhibit normal cholesterol metabolism. Further knockdown of Cyb5a in L-Cyb5b−/− (L-Cyb5b−/−/short hairpin [sh]Cyb5a) mice leads to a marked accumulation of T-MAS and dihydro-T-MAS, indicating that either CYB5A or CYB5B is required for sterol C4-demethylation. The L-Cyb5b−/−/shCyb5a mice are largely normal, with lower sterol regulatory element-binding protein (SREBP)-target gene expression during refeeding and higher liver triglyceride levels while fasting, as T-MAS and dihydro-T-MAS inhibit the SREBP pathway and activate the PPARγ pathway. In summary, CYB5A and CYB5B compensate for sterol C4-demethylation, and T-MAS and dihydro-T-MAS can modulate the SREBP and PPARγ pathways. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2211-1247 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2211124724012634; https://doaj.org/toc/2211-1247 |
| DOI: |
10.1016/j.celrep.2024.114912 |
| URL الوصول: |
https://doaj.org/article/a35ab4c267324c2da2eef4f0ee6f882b |
| رقم الانضمام: |
edsdoj.35ab4c267324c2da2eef4f0ee6f882b |
| قاعدة البيانات: |
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