Department of Biological Sciences.
Center for Protein Conformational Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania.
Curr Opin Lipidol. 2024 Oct 1;35(5):248-252. doi: 10.1097/MOL.0000000000000943. Epub 2024 Aug 22.
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.
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.
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.
本综述探讨了脂肪诱导转录物 2（FIT2）蛋白在脂滴（LD）生物学中的作用及其在细胞生理学和疾病中的广泛影响。随着对 FIT2 功能在各种模型系统中的理解的最新进展，本综述及时综合了其机制和生理意义。
FIT2 是一种内质网（ER）驻留蛋白，已被确定为从酵母到哺乳动物等多种生物中 LD 形成的关键调节剂。它通过隔离二酰基甘油（DAG）并可能影响 ER 膜动力学来促进 LD 的生物发生。除了在脂质代谢中的作用外，FIT2 还与 ER 相关降解（ERAD）交叉，对蛋白质稳态至关重要，并与未折叠蛋白反应（UPR）相关。FIT2 的失调也与代谢紊乱有关，如胰岛素抵抗和脂肪营养不良，突出了其临床相关性。
对 FIT2 功能的深入了解强调了其在 LD 形成和脂质稳态中的关键作用。了解其在 ER 蛋白稳态和极低密度脂蛋白生物发生中的参与，对代谢疾病和癌症具有广泛的意义。针对 FIT2 的治疗策略可能为调节脂质代谢和减轻相关病理提供新的方法。需要进一步研究以阐明 FIT2 在细胞脂质和蛋白质网络中的全部相互作用，可能为代谢和 ER 应激相关疾病开辟新的治疗途径。
