线粒体脂肪酸氧化功能障碍通过ATP缺乏引起的溶酶体pH异常损害了自流
Yan-Yu Zhang1, Ze-Dong Lv1, Mai Wang1
1LANEH, School of Life Sciences, East China Normal University, Shanghai, China.
The Journal of nutritional biochemistry
|May 4, 2025
概括
线粒体脂肪酸氧化 (FAO) 功能障碍破坏了 lysosomal 酸化,损害了自降解. 这项研究揭示了粮农组织的粮农组织.
科学领域:
- 细胞生物学 细胞生物学
- 线粒体功能的功能
- 自学研究 自学研究
背景情况:
- 自对于细胞平衡和能量代谢至关重要.
- 线粒体脂肪酸氧化 (FAO) 对细胞能量生产至关重要.
- 线粒体FAO功能障碍对自的影响仍然不太清楚.
研究的目的:
- 研究线粒体FAO调节自过程中的调节作用和潜在机制.
- 阐明 mitochondrial FAO 功能障碍如何影响自开始,降解和 lysosomal 功能.
主要方法:
- 利用尼罗河鱼 (Oreochromis niloticus) 作为一个模型生物.
- 通过饮食中的米尔德罗纳特和卡尼丁棕甲基转移酶1a knockdown 抑制线粒体FAO.
- 分析了自标记物,溶酶体特性,ATP水平和关键信号通路 (AMPK/LKB1,PPARα,RXRα,TFEB).
主要成果:
- 线粒体FAO抑制增强了自开始和溶酶体增殖,但降低了降解活性.
- lysosomal 酸化受损,导致由于v-ATPase 失衡和ATP 缺乏导致化.
- 抑制降低了ATP的产生,并提高了AMP/ATP的比率,通过AMPK/LKB1通路激活了自.
- PPARα和RXRα的上调促进了TFEB表达,影响了与自相关的基因转录.
结论:
- 线粒体FAO功能障碍通过扰乱 lysosomal 酸化来损害自流.
- 这种功能障碍影响细胞能量状态 (ATP水平) 并激活自启动通路.
- 线粒体FAO对于维持 lysosomal 稳态和适当的自流至关重要.
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