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在肝脏疾病中,线粒体功能障碍和肝细胞亡通过氧化应激,翻译后修饰,炎症和肠道屏障功能障碍在肝脏疾病中的作用

Karli R LeFort¹, Wiramon Rungratanawanich², Byoung-Joon Song³

¹Section of Molecular Pharmacology and Toxicology, National Institute on Alcohol Abuse and Alcoholism, 9000 Rockville Pike, Bethesda, MD, 20892, USA. Karli.LeFort@nih.gov.

Cellular and molecular life sciences : CMLS

|January 12, 2024

概括

线粒体功能障碍驱动肝细胞亡在肝脏疾病,如ALD,MASLD和DILI. 了解这些分子机制是开发肝纤维化和肝硬化向治疗的关键.

科学领域:

肝病学肝病学是一种肝病学.
线粒体生物学线粒体生物学
疾病的分子机制.

背景情况:

线粒体功能障碍和肝细胞亡是肝脏疾病的核心,例如与酒精相关的肝病 (ALD),与代谢功能障碍相关的脂肪性肝病 (MASLD) 和药物诱导的肝损伤 (DILI).
乙醇诱导性细胞染色体P450-2E1 (CYP2E1) 代谢酒精和异生菌,产生有毒代谢物,诱导氧化应激并损害线粒体和内 плазма网状细胞等器官.
线粒体中的氧化应激导致细胞组件的共性修饰和线粒体蛋白质的翻译后修饰 (PTMs),影响关键的代谢和亡途径.

研究的目的:

审查最近关于将线粒体功能障碍与各种肝脏疾病中的肝细胞亡联系起来的分子机制的发现.
突出线粒体在调节肝脏平衡,炎症和细胞死亡中的关键信号通路中的作用.
为开发针对肝脏疾病的向治疗策略提供基础.

主要方法:

基本,翻译和临床研究的审查.
分析涉及线粒体功能障碍,氧化应激和亡的分子机制.
检查CYP2E1和异生物代谢在肝损伤中的作用.

主要成果:

由氧化应激和改变的PTMs驱动的线粒体功能障碍,使能量代谢和线粒体代谢至关重要的酶失活,导致肝细胞亡.
线粒体调节生物能学,炎症和细胞死亡的关键信号级联,它们的调节失调有助于肝细胞死亡.
改变的线粒体平衡促进炎症和肝星细胞激活,导致肝纤维化和肝硬化.

结论:

线粒体功能障碍是各种肝脏疾病中肝细胞亡的关键因素.
准线粒体通路为治疗肝纤维化和肝硬化提供了一个有希望的治疗途径.
进一步研究复杂的分子机制对于有效的治疗开发至关重要.

关键词:

这就是ALDH2的原因.与酒精相关的肝脏疾病细胞灭亡 (apoptosis) 是一种死亡的过程.在CYP2E1中.药物诱导的肝损伤是药物诱导的末端毒性病 (Endotoxemia) 是一种导致内毒性病的疾病.肠肝轴肠肝轴肠道屏障功能障碍肠道屏障功能障碍与代谢功能障碍相关的脂肪性肝病.微生物群中的微生物群.线粒体功能障碍线粒体功能障碍氧化应激是一种氧化应激.后翻译修改后的修改.病毒性肝炎的病毒性肝炎.

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