AT-1 is the ER membrane acetyl-CoA transporter and is essential for cell viability
AT-1 is the ER membrane acetyl-CoA transporter and is essential for cell viability
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DOI：
10.1242/jcs.068841
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发表时间：
2010-10-01
影响因子：
4
通讯作者：
Puglielli, Luigi
中科院分区：
文献类型：
--
作者：
Jonas, Mary Cabell;Pehar, Mariana;Puglielli, Luigi
在早期分泌途径中新生蛋白质的瞬时或永久性修饰是一种重要的细胞功能，它确保了膜蛋白和分泌蛋白的正确折叠和成熟。我们最近描述了一种膜蛋白β - 位点APP切割酶1（BACE1）的新型翻译后调控形式，涉及内质网（ER）腔内的瞬时赖氨酸乙酰化。这一过程的关键组分是两种基于内质网的乙酰辅酶A：赖氨酸乙酰转移酶，即ATase1和ATase2，以及一种将乙酰辅酶A转运到内质网腔的膜转运蛋白。在此，我们报道了乙酰辅酶A转运蛋白1（AT - 1）作为内质网膜乙酰辅酶A转运蛋白的功能鉴定。我们表明AT - 1调节内质网转运蛋白的乙酰化状态，包括膜蛋白BACE1、低密度脂蛋白受体和淀粉样前体蛋白（APP）。最后，我们表明AT - 1对细胞活力至关重要，因为其下调会导致广泛的细胞死亡以及自噬特征的诱导。
The transient or permanent modification of nascent proteins in the early secretory pathway is an essential cellular function that ensures correct folding and maturation of membrane and secreted proteins. We have recently described a new form of post-translational regulation of the membrane protein beta-site APP cleaving enzyme 1 (BACE1) involving transient lysine acetylation in the lumen of the endoplasmic reticulum (ER). The essential components of this process are two ER-based acetyl-CoA: lysine acetyltransferases, ATase1 and ATase2, and a membrane transporter that translocates acetyl-CoA into the lumen of the ER. Here, we report the functional identification of acetyl-CoA transporter 1 (AT-1) as the ER membrane acetyl-CoA transporter. We show that AT-1 regulates the acetylation status of ER-transiting proteins, including the membrane proteins BACE1, low-density lipoprotein receptor and amyloid precursor protein (APP). Finally, we show that AT-1 is essential for cell viability as its downregulation results in widespread cell death and induction of features characteristic of autophagy.