Protein acylation by saturated very long chain fatty acids and endocytosis are involved in necroptosis.
Protein acylation by saturated very long chain fatty acids and endocytosis are involved in necroptosis.
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DOI：
10.1016/j.chembiol.2021.03.012
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发表时间：
2021-09-16
影响因子：
8.6
通讯作者：
Atilla-Gokcumen GE
中科院分区：
文献类型：
--
作者：
Pradhan AJ;Lu D;Parisi LR;Shen S;Berhane IA;Galster SL;Bynum K;Monje-Galvan V;Gokcumen O;Chemler SR;Qu J;Kay JG;Atilla-Gokcumen GE
坏死性凋亡是细胞死亡的一种形式，其特征是受体相互作用蛋白激酶 (RIPK) 活性和通过混合谱系激酶样蛋白 (MLKL) 实现质膜透化。这种透化作用是导致坏死性凋亡的炎症特性的原因。我们之前表明，极长链脂肪酸（VLCFA）可能通过蛋白质脂肪酰化在功能上参与坏死性凋亡。在这里，我们定义了坏死性凋亡期间饱和 VLCFA 的蛋白质酰化范围。我们发现，膜透化的关键 MLKL 和磷酸化 MLKL 在坏死性凋亡过程中完全被酰化。降低 VLCFA 的水平会减少它们的膜募集，这表明 VLCFA 的酰化有助于它们的膜定位。磷酸MLKL 的酰化发生在磷酸化和寡聚化的下游，并且似乎部分由ZDHHC5（一种棕榈酰转移酶）介导。我们还表明，内体运输的破坏会增加坏死性凋亡期间的细胞活力，这可能是通过阻止磷酸MLKL从质膜上的募集或去除来实现的。普拉丹等人。表明 MLKL 和 pMLKL 在坏死性凋亡过程中被饱和超长链脂肪酸酰化，并且内吞作用的破坏降低了膜结合的 pMLKL 和 MLKL 的水平，从而在该过程中挽救了细胞死亡。
Necroptosis is a form of cell death characterized by receptor interacting protein kinase (RIPK) activity and plasma membrane permeabilization via mixed lineage kinase like protein (MLKL). This permeabilization is responsible for the inflammatory properties of necroptosis. We previously showed that very long chain fatty acids (VLCFAs) are functionally involved in necroptosis, potentially through protein fatty acylation. Here, we define the scope of protein acylation by saturated VLCFAs during necroptosis. We show that MLKL and phosphoMLKL, key for membrane permeabilization, are exclusively acylated during necroptosis. Reducing the levels of VLCFAs decreases their membrane recruitment, suggesting that acylation by VLCFAs contributes to their membrane localization. Acylation of phosphoMLKL occurs downstream of phosphorylation and oligomerization and appears to be, in part, mediated by ZDHHC5 (a palmitoyl transferase). We also show that disruption of endosomal trafficking increases cell viability during necroptosis, possibly by preventing recruitment, or removal, of phosphoMLKL from the plasma membrane. Pradhan et al. show that MLKL and pMLKL are acylated by saturated very long chain fatty acids during necroptosis and that the disruption of endocytosis decreases the levels of membrane bound pMLKL and MLKL, resulting a rescue from cell death during this process.
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影响因子：
3.4
作者：
Gilbert, Robert J. C.
通讯作者：
Gilbert, Robert J. C.
DOI：
10.1007/978-1-4939-9532-5_16
发表时间：
2019-01-01
期刊：
PROTEIN LIPIDATION: METHODS AND PROTOCOLS
影响因子：
--
作者：
Blanc, Mathieu;David, Fabrice P. A.;van der Goot, F. Gisou
通讯作者：
van der Goot, F. Gisou
影响因子：
8.8
作者：
Dondelinger, Yves;Declercq, Wim;Vandenabeele, Peter
通讯作者：
Vandenabeele, Peter
影响因子：
7.7
作者：
Hilgemann DW;Fine M;Linder ME;Jennings BC;Lin MJ
通讯作者：
Lin MJ
影响因子：
64.5
作者：
Gong YN;Guy C;Olauson H;Becker JU;Yang M;Fitzgerald P;Linkermann A;Green DR
通讯作者：
Green DR