Molecular mechanisms of perilipin protein function in lipid droplet metabolism,FEBS Letters

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Molecular mechanisms of perilipin protein function in lipid droplet metabolism
FEBS Letters ( IF 3.0 ) Pub Date : 2023-12-23 , DOI: 10.1002/1873-3468.14792
Elena Griseti ₁ , Abdoul Akim Bello ₂ , Eric Bieth _{1,

3} , Bayane Sabbagh ₄ , Jason S Iacovoni ₁ , Joëlle Bigay ₂ , Henrik Laurell ₁ , Alenka Čopič ₄

Affiliation

Perilipins are abundant lipid droplet (LD) proteins present in all metazoans and also in Amoebozoa and fungi. Humans express five perilipins, which share a similar domain organization: an amino-terminal PAT domain and an 11-mer repeat region, which can fold into amphipathic helices that interact with LDs, followed by a structured carboxy-terminal domain. Variations of this organization that arose during vertebrate evolution allow for functional specialization between perilipins in relation to the metabolic needs of different tissues. We discuss how different features of perilipins influence their interaction with LDs and their cellular targeting. PLIN1 and PLIN5 play a direct role in lipolysis by regulating the recruitment of lipases to LDs and LD interaction with mitochondria. Other perilipins, particularly PLIN2, appear to protect LDs from lipolysis, but the molecular mechanism is not clear. PLIN4 stands out with its long repetitive region, whereas PLIN3 is most widely expressed and is used as a nascent LD marker. Finally, we discuss the genetic variability in perilipins in connection with metabolic disease, prominent for PLIN1 and PLIN4, underlying the importance of understanding the molecular function of perilipins.

中文翻译：

脂滴代谢中周脂质蛋白功能的分子机制

Perilipins 是一种丰富的脂滴 (LD) 蛋白，存在于所有后生动物以及变形虫和真菌中。人类表达五种 perilipin，它们具有相似的结构域组织：一个氨基末端 PAT 结构域和一个 11 聚体重复区域，该区域可以折叠成与 LD 相互作用的两亲性螺旋，然后是一个结构化的羧基末端结构域。脊椎动物进化过程中出现的这种组织的变异使得周脂质之间能够根据不同组织的代谢需求实现功能专门化。我们讨论了 perilipins 的不同特征如何影响它们与 LD 的相互作用及其细胞靶向。 PLIN1 和 PLIN5 通过调节脂肪酶向 LD 的募集以及 LD 与线粒体的相互作用，在脂肪分解中发挥直接作用。其他周脂质，特别是 PLIN2，似乎可以保护 LD 免于脂肪分解，但分子机制尚不清楚。 PLIN4 因其长重复区域而脱颖而出，而 PLIN3 表达最广泛，并被用作新生的 LD 标记。最后，我们讨论了与代谢疾病相关的 perilipins 的遗传变异，其中 PLIN1 和 PLIN4 尤为突出，这奠定了了解 perilipins 分子功能的重要性。

更新日期：2023-12-23

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