非典型的卡德林脂肪直接调节线粒体功能和代谢状态
Anson Sing1, Yonit Tsatskis2, Lacramioara Fabian3
1Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Cell
|September 13, 2014
概括
脂肪干对线粒体功能至关重要,直接调节电子运输链. 脂肪卡德林的损失会损害氧化酸化,并促进有氧糖解,独立于Hippo和PCP通路.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 分子生物学分子生物学
背景情况:
- 脂肪 (Ft) 干是大型细胞粘附分子,参与希波信号和平面细胞极性.
- 突变在Ftcadherins与各种瘤有关,被认为是由于Hippo或PCP通路缺陷.
研究的目的:
- 为了研究Drosophila脂肪在细胞新陈代谢中的新型作用.
- 为了确定脂肪卡德林是否直接影响线粒体功能.
主要方法:
- 研究了脂肪卡德林的亚细胞局部.
- 分析了脂肪卡德林损失对线粒体电子运输链 (ETC) 活动的影响.
- 评估反应性氧物种 (ROS) 生产和 ft.突变物中的代谢转变.
主要成果:
- 脂肪卡德林被蛋白质分解分离,释放出线粒体进口的片段 (Ft).
- Ft ((mito) 直接与Ndufv2结合,稳定了ETC的复合物I.
- 失去Ft导致I复合体活动受损,ROS增加,以及代谢转换为有氧糖解 (Warburg效应).
结论:
- 果脂肪干在调节线粒体的完整性和功能方面发挥着直接的,非正规的作用.
- 脚突变体中的线粒体缺陷独立于Hippo和PCP信号传输.
- 脂肪卡德林代表了理解和治疗癌症代谢失调的潜在新目标.
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