Lipid signaling on the mitochondrial surface.

Lipid signaling on the mitochondrial surface.
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DOI:
10.1016/j.bbalip.2009.05.012
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发表时间:
2009-09
影响因子:
4.8
通讯作者:
Frohman, Michael A.
Frohman, Michael A.
中科院分区:
生物学2区
文献类型:
--
作者:
Huang, Huiyan;Frohman, Michael A.

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信号脂质磷脂酸 (PA)、二酰甘油 (DAG) 和磷脂酰肌醇 4,5-二磷酸 (PI4,5P2) 的调节产生和消除创建了一个复杂且相互关联的信号网络,可调节多种真核细胞生物事件。经典磷脂酶 D (PLD) 通过水解磷脂酰胆碱 (PC) 在质膜和运输膜细胞器上产生 PA 已得到广泛研究。在本章中,我们回顾了 PLD 超家族中新发现的非经典成员 MitoPLD,它定位于线粒体表面,并通过心磷脂 (CL) 水解生成 PA 在线粒体融合中发挥作用。鉴于经典 PLD 生成的 PA 在促进 SNARE 介导的分泌膜囊泡融合到质膜中的作用,PA 在促进由称为 Mitofusins 的蛋白质进行的线粒体融合事件中的作用很有趣。然而,此外,线粒体表面的 PA 还可能触发信号级联,从而提升 DAG,从而导致影响线粒体裂变和能量产生的下游事件。线粒体表面的 PA 产生也可能刺激局部产生 PI4,5P2,以促进线粒体裂变和亚细胞运输或促进 Ca2+ 流入。
Regulated production and elimination of the signaling lipids phosphatidic acid (PA), diacylglycerol (DAG), and phosphatidylinositol 4,5-bisphosphate (PI4,5P2) creates a complex and interconnected signaling network that modulates a wide variety of eukaryotic cell biological events. PA production at the plasma membrane and on trafficking membrane organelles by classical Phospholipase D (PLD) through the hydrolysis of phosphatidylcholine (PC) has been studied widely. In this chapter, we review a newly identified, non-canonical member of the PLD superfamily, MitoPLD, which localizes to the mitochondrial surface and plays a role in mitochondrial fusion via the hydrolysis of cardiolipin (CL) to generate PA. The role of PA in facilitating the mitochondrial fusion event carried out by proteins known as Mitofusins is intriguing in light of the role classic PLD-generated PA plays in facilitating SNARE-mediated fusion of secretory membrane vesicles into the plasma membrane. In addition, however, PA on the mitochondrial surface may also trigger a signaling cascade that elevates DAG, leading to downstream events that affect mitochondrial fission and energy production. PA production on the mitochondrial surface may also stimulate local production of PI4,5P2 to facilitate mitochondrial fission and subcellular trafficking or facilitate Ca2+ influx.
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