Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, Kansas.
Am J Physiol Cell Physiol. 2022 Oct 1;323(4):C1100-C1111. doi: 10.1152/ajpcell.00281.2022. Epub 2022 Sep 5.
Mechanistic target of rapamycin (mTOR) is a serine-threonine kinase and a cellular sensor for nutrient and energy status, which is critical in regulating cell metabolism and growth by governing the anabolic (protein and lipid synthesis) and catabolic process (autophagy). Alcohol-associated liver disease (ALD) is a major chronic liver disease worldwide that carries a huge financial burden. The spectrum of the pathogenesis of ALD includes steatosis, fibrosis, inflammation, ductular reaction, and eventual hepatocellular carcinoma, which is closely associated with metabolic changes that are regulated by mTOR. In this review, we summarized recent progress of alcohol consumption on the changes of mTORC1 and mTORC2 activity, the potential mechanisms and possible impact of the mTORC1 changes on autophagy in ALD. We also discussed the potential beneficial effects and limitations of targeting mTORC1 against ALD.
雷帕霉素靶蛋白(mTOR)是一种丝氨酸-苏氨酸激酶,也是一种细胞营养和能量状态传感器,通过调节合成代谢(蛋白质和脂质合成)和分解代谢(自噬)过程,在调节细胞代谢和生长方面起着关键作用。酒精相关性肝病(ALD)是全球范围内的一种主要慢性肝病,给经济带来了巨大的负担。ALD 的发病机制谱包括脂肪变性、纤维化、炎症、小管反应和最终的肝细胞癌,这与受 mTOR 调节的代谢变化密切相关。在这篇综述中,我们总结了最近关于酒精摄入对 mTORC1 和 mTORC2 活性变化的研究进展,以及 mTORC1 变化对 ALD 中自噬的潜在机制和可能影响。我们还讨论了针对 mTORC1 治疗 ALD 的潜在有益效果和局限性。