Regulation of Signaling and Metabolism by Lipin-mediated Phosphatidic Acid Phosphohydrolase Activity.
Regulation of Signaling and Metabolism by Lipin-mediated Phosphatidic Acid Phosphohydrolase Activity.
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DOI：
10.3390/biom10101386
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发表时间：
2020-09-29
期刊：
影响因子：
5.5
通讯作者：
Finck BN
中科院分区：
文献类型：
--
作者：
Lutkewitte AJ;Finck BN
磷脂酸（PA）是甘油三酯合成途径中的甘油磷脂中间体，其作为细胞膜的组分具有令人难以置信的重要结构功能，并且对细胞内和细胞间信号传导途径具有动态影响。虽然有许多途径来合成和降解PA，但产生二酰基甘油的PA磷酸水解酶家族（脂蛋白家族蛋白）构成PA掺入甘油三酯的主要途径。以前，人们认为用于合成甘油三酯的PA池是不同的，区室化的，并且与信号传导途径没有广泛交叉。然而，我们现在知道，调节lipin 1的活性对各种细胞类型的信号传导有深远的影响。事实上，在除脂肪组织外的大多数组织中，脂蛋白介导的PA磷酸水解酶活性远不限制甘油三酯合成的正常速率，而是影响控制细胞稳态的关键信号级联。在这篇综述中，我们将讨论脂蛋白介导的PA浓度控制如何调节哺乳动物生物体的代谢和信号。
Phosphatidic acid (PA) is a glycerophospholipid intermediate in the triglyceride synthesis pathway that has incredibly important structural functions as a component of cell membranes and dynamic effects on intracellular and intercellular signaling pathways. Although there are many pathways to synthesize and degrade PA, a family of PA phosphohydrolases (lipin family proteins) that generate diacylglycerol constitute the primary pathway for PA incorporation into triglycerides. Previously, it was believed that the pool of PA used to synthesize triglyceride was distinct, compartmentalized, and did not widely intersect with signaling pathways. However, we now know that modulating the activity of lipin 1 has profound effects on signaling in a variety of cell types. Indeed, in most tissues except adipose tissue, lipin-mediated PA phosphohydrolase activity is far from limiting for normal rates of triglyceride synthesis, but rather impacts critical signaling cascades that control cellular homeostasis. In this review, we will discuss how lipin-mediated control of PA concentrations regulates metabolism and signaling in mammalian organisms.
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