The emerging role of fat-inducing transcript 2 in endoplasmic reticulum proteostasis and lipoprotein biogenesis.

IF 3.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Current opinion in lipidology Pub Date : 2024-10-01 Epub Date: 2024-08-22 DOI:10.1097/MOL.0000000000000943
Jeffrey L Brodsky, Anuradha Iyer, Konstantinos I Fortounas, Edward A Fisher
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Abstract

Purpose of review: This review examines the evolving role of the fat-inducing transcript 2 (FIT2) protein in lipid droplet (LD) biology and its broader implications in cellular physiology and disease. With recent advancements in understanding FIT2 function across various model systems, this review provides a timely synthesis of its mechanisms and physiological significance.

Recent findings: FIT2, an endoplasmic reticulum (ER)-resident protein, has been established as a critical regulator of LD formation in diverse organisms, from yeast to mammals. It facilitates LD biogenesis by sequestering diacylglycerol (DAG) and potentially influencing ER membrane dynamics. Beyond its role in lipid metabolism, FIT2 intersects with the ER-associated degradation (ERAD), is critical for protein homeostasis, and is linked to the unfolded protein response (UPR). Dysregulation of FIT2 has also been linked to metabolic disorders such as insulin resistance and lipodystrophy, highlighting its clinical relevance.

Summary: Insights into FIT2 function underscore its pivotal role in LD formation and lipid homeostasis. Understanding its involvement in ER proteostasis and very low density lipoprotein biogenesis has broad implications for metabolic diseases and cancer. Therapeutic strategies targeting FIT2 may offer novel approaches to modulate lipid metabolism and mitigate associated pathologies. Further research is needed to elucidate the full spectrum of FIT2's interactions within cellular lipid and protein networks, potentially uncovering new therapeutic avenues for metabolic and ER stress-related disorders.

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脂肪诱导转录本 2 在内质网蛋白稳态和脂蛋白生物生成过程中的新作用。
综述的目的:本综述探讨了脂肪诱导转录本 2(FIT2)蛋白在脂滴(LD)生物学中不断演变的作用及其在细胞生理学和疾病中的广泛意义。最近,人们对 FIT2 在各种模型系统中的功能有了更深入的了解,本综述对其作用机制和生理意义进行了及时的综述:FIT2是一种内质网(ER)驻留蛋白,已被证实是从酵母到哺乳动物等多种生物体内LD形成的关键调节因子。它通过螯合二酰甘油(DAG)和潜在地影响ER膜动力学来促进LD的生物生成。除了在脂质代谢中的作用外,FIT2 还与ER相关降解(ERAD)相互交叉,对蛋白质平衡至关重要,并与未折叠蛋白反应(UPR)有关。FIT2 的功能失调还与胰岛素抵抗和脂肪营养不良等代谢紊乱有关,这突显了它的临床相关性。了解 FIT2 参与 ER 蛋白稳态和极低密度脂蛋白的生物生成对代谢性疾病和癌症具有广泛的影响。针对 FIT2 的治疗策略可为调节脂质代谢和减轻相关病症提供新的方法。还需要进一步的研究来阐明 FIT2 在细胞脂质和蛋白质网络中的全方位相互作用,从而为代谢和 ER 应激相关疾病找到新的治疗途径。
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来源期刊
Current opinion in lipidology
Current opinion in lipidology 医学-内分泌学与代谢
CiteScore
6.70
自引率
4.50%
发文量
64
审稿时长
6-12 weeks
期刊介绍: With its easy-to-digest reviews on important advances in world literature, Current Opinion in Lipidology offers expert evaluation on a wide range of topics from six key disciplines including nutrition and metabolism, genetics and molecular biology, and hyperlipidaemia and cardiovascular disease. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by a section of Bimonthly Updates, which deliver an insight into new developments at the cutting edge of the disciplines covered in the journal.
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