Regulation of Liver Metabolism by Autophagy.
Regulation of Liver Metabolism by Autophagy.
复制标题
通过自噬调节肝脏代谢。
DOI：
10.1053/j.gastro.2015.09.042
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发表时间：
2016-02
期刊：
影响因子：
29.4
通讯作者：
Cuervo AM
中科院分区：
文献类型：
--
作者：
Madrigal-Matute J;Cuervo AM
细胞内的成分必须循环利用，以保持细胞的能量，并确保蛋白质和细胞器的质量控制。自噬是一种高度保守的循环过程，涉及溶酶体中细胞成分的降解。虽然自噬调节了许多细胞功能，但它首先被发现维持肝细胞的能量平衡。随着我们对自噬的了解增加，我们发现它与肝细胞中的能量调节之间的联系是紧密而复杂的。我们回顾了肝脏自噬监测和调节细胞代谢的三种机制。自噬提供了满足细胞能量需求所需的基本成分(氨基酸、脂肪和碳水化合物)，它还通过控制线粒体的数量、质量和动态来调节能量供应。最后，自噬还调节代谢途径中的酶水平。鉴于自噬参与控制肝脏代谢的多种方式，毫不奇怪，自噬的失调与肥胖症、糖尿病或代谢综合征等代谢性疾病以及脂肪肝、非酒精性脂肪性肝炎和肝细胞癌等肝脏特异性疾病有关。我们讨论了其中的一些联系，以及肝脏自噬如何作为常见代谢紊乱的治疗靶点。
Intracellular components must be recycled for cells to maintain energy and ensure quality control of proteins and organelles. Autophagy is a highly conserved recycling process that involves degradation of cellular constituents in lysosomes. Although autophagy regulates a number of cell functions, it was first found to maintain energy balance in liver cells. As our understanding of autophagy has increased, we have found its connections to energy regulation in liver cells to be tight and complex. We review three mechanisms by which hepatic autophagy monitors and regulates cellular metabolism. Autophagy provides essential components (amino acids, lipids and carbohydrates) required to meet the cell’s energy needs, and it also regulates energy supply by controlling the number, quality, and dynamics of the mitochondria. Lastly, autophagy also modulates levels of enzymes in metabolic pathways. In light of the multiple ways in which autophagy participates to control liver metabolism, it is no surprise that dysregulation of autophagy has been associated with metabolic diseases such as obesity, diabetes, or metabolic syndrome, as well as liver-specific disorders such as fatty liver, non-alcoholic steatohepatitis and hepatocellular carcinoma. We discuss some of these connections and how hepatic autophagy might serve as a therapeutic target in common metabolic disorders.