Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Korea.
BK21 FOUR KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu 41944, Korea.
Cells. 2022 Feb 10;11(4):620. doi: 10.3390/cells11040620.
Autophagy is an adaptive self-eating process involved in degradation of various cellular components such as carbohydrates, lipids, proteins, and organelles. Its activity plays an essential role in tissue homeostasis and systemic metabolism in response to diverse challenges, including nutrient depletion, pathogen invasion, and accumulations of toxic materials. Therefore, autophagy dysfunctions are intimately associated with many human diseases such as cancer, neurodegeneration, obesity, diabetes, infection, and aging. Although its acute post-translational regulation is well described, recent studies have also shown that autophagy can be controlled at the transcriptional and post-transcriptional levels. Nuclear receptors (NRs) are in general ligand-dependent transcription factors consisting of 48 members in humans. These receptors extensively control transcription of a variety of genes involved in development, metabolism, and inflammation. In this review, we discuss the roles and mechanisms of NRs in an aspect of transcriptional regulation of hepatic autophagy, and how the NR-driven autophagy pathway can be harnessed to treat various liver diseases.
自噬是一种参与降解碳水化合物、脂质、蛋白质和细胞器等各种细胞成分的适应性自我吞噬过程。它的活性在组织稳态和全身代谢中起着至关重要的作用,以应对各种挑战,包括营养物质耗竭、病原体入侵和有毒物质的积累。因此,自噬功能障碍与许多人类疾病密切相关,如癌症、神经退行性疾病、肥胖症、糖尿病、感染和衰老。尽管自噬的急性翻译后调控已得到很好的描述,但最近的研究也表明,自噬可以在转录和转录后水平上进行控制。核受体 (NRs) 通常是配体依赖性转录因子,人类有 48 个成员。这些受体广泛控制着参与发育、代谢和炎症的多种基因的转录。在这篇综述中,我们讨论了 NRs 在肝脏自噬的转录调控方面的作用和机制,以及如何利用 NR 驱动的自噬途径来治疗各种肝脏疾病。