The NTPase activity of the double FYVE domain-containing protein 1 regulates lipid droplet metabolism.
The NTPase activity of the double FYVE domain-containing protein 1 regulates lipid droplet metabolism.
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双FYVE结构域蛋白1的NTPase活性调节脂质滴剂代谢。
DOI：
10.1016/j.jbc.2022.102830
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发表时间：
2023-02
影响因子：
4.8
通讯作者：
Kast, D. J.
中科院分区：
文献类型：
--
作者：
Ismail, V. A.;Naismith, T.;Kast, D. J.
脂滴（LDs）是一种短暂的脂质储存细胞器，可以很容易地利用它来为细胞补充能量或脂质结构单元，因此在细胞代谢中起着核心作用。然而，调节LD生长和降解的分子因素和潜在机制知之甚少。已经发现，在LD和内质网之间建立接触的蛋白质在调节LD代谢中起关键作用。近年来，自噬相关蛋白--含双FYVE结构域的蛋白1（DFCP 1/ZFYVE 1）被发现存在于内质网和LD的界面，但DFCP 1在自噬和LD代谢中的作用尚不清楚。在这里，我们表明，DFCP 1是一种新的NTR，调节游离脂肪酸代谢。具体来说，我们表明，DFPC 1敲低，特别是在饥饿期间，增加细胞游离脂肪酸和降低细胞TAG的水平，导致累积的小LD。使用选择性截短，我们证明，DFCP 1积累LD在细胞和体外调节由以前未知的NTR域。使用光谱方法，我们表明，这NTR结构域可以二聚化，可以水解ATP和GTP。此外，影响核苷酸水解或二聚化的DFCP 1突变导致LD上DFCP 1积累的变化、LD密度和大小的变化以及LD与自噬体的共定位。总的来说，我们的研究结果表明，DFCP 1是一种NTR，它调节细胞中LD的代谢。
Lipid droplets (LDs) are transient lipid storage organelles that can be readily tapped to resupply cells with energy or lipid building blocks and therefore play a central role in cellular metabolism. However, the molecular factors and underlying mechanisms that regulate the growth and degradation of LDs are poorly understood. It has emerged that proteins that establish contacts between LDs and the endoplasmic reticulum play a critical role in regulating LD metabolism. Recently, the autophagy-related protein, double FYVE domain–containing protein 1 (DFCP1/ZFYVE1) was shown to reside at the interface of the endoplasmic reticulum and LDs, however, little is known about the involvement of DFCP1 in autophagy and LD metabolism. Here, we show that DFCP1 is a novel NTPase that regulates free fatty acid metabolism. Specifically, we show that DFPC1-knockdown, particularly during starvation, increases cellular free fatty acids and decreases the levels of cellular TAGs, resulting in accumulated small LDs. Using selective truncations, we demonstrate that DFCP1 accumulation on LDs in cells and in vitro is regulated by a previously unknown NTPase domain. Using spectroscopic approaches, we show that this NTPase domain can dimerize and can hydrolyze both ATP and GTP. Furthermore, mutations in DFCP1 that either impact nucleotide hydrolysis or dimerization result in changes in the accumulation of DFCP1 on LDs, changes in LD density and size, and colocalization of LDs to autophagosomes. Collectively, our findings suggest that DFCP1 is an NTPase that modulates the metabolism of LDs in cells.
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影响因子：
11.1
作者：
Krahmer, Natalie;Farese, Robert V., Jr.;Walther, Tobias C.
通讯作者：
Walther, Tobias C.
突变动力蛋白的诱导特异性阻断内吞涂层囊泡的形成。
影响因子：
7.8
作者：
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Schmid, S L
DOI：
10.1016/j.bbalip.2017.06.008
发表时间：
2017-10
期刊：
Biochimica et biophysica acta. Molecular and cell biology of lipids
影响因子：
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作者：
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通讯作者：
Mashek DG
影响因子：
4.8
作者：
Matveeva, EA;He, P;Whiteheart, SW
通讯作者：
Whiteheart, SW
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影响因子：
16.6
作者：
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通讯作者：
Delmas D