Institute for Medical Research and Occupational Health, Biochemistry and Organic Analytical Chemistry Unit, Zagreb, Croatia.
Arh Hig Rada Toksikol. 2023 Jun 26;74(2):75-89. doi: 10.2478/aiht-2023-74-3723. eCollection 2023 Jun 1.
This paper brings a brief review of the human patatin-like phospholipase domain-containing protein (PNPLA) family. Even though it consists of only nine members, their physiological roles and mechanisms of their catalytic activity are not fully understood. However, the results of a number of knock-out and gain- or loss-of-function research models suggest that these enzymes have an important role in maintaining the homeostasis and integrity of organelle membranes, in cell growth, signalling, cell death, and the metabolism of lipids such as triacylglycerol, phospholipids, ceramides, and retinyl esters. Research has also revealed a connection between PNPLA family member mutations or irregular catalytic activity and the development of various diseases. Here we summarise important findings published so far and discuss their structure, localisation in the cell, distribution in the tissues, specificity for substrates, and their potential physiological role, especially in view of their potential as drug targets.
本文简要综述了人 patatin 样磷脂酶结构域蛋白（PNPLA）家族。尽管该家族仅由 9 个成员组成，但它们的生理作用及其催化活性的机制尚不完全清楚。然而，许多敲除和获得或丧失功能的研究模型的结果表明，这些酶在维持细胞器膜的动态平衡和完整性、细胞生长、信号转导、细胞死亡以及甘油三酯、磷脂、神经酰胺和视黄醇酯等脂质代谢中具有重要作用。研究还揭示了 PNPLA 家族成员突变或异常催化活性与各种疾病发展之间的联系。在这里，我们总结了迄今为止发表的重要研究结果，并讨论了它们的结构、在细胞中的定位、在组织中的分布、对底物的特异性以及它们的潜在生理作用，特别是考虑到它们作为药物靶点的潜力。
