Phosphorylation and cleavage of presenilin-associated rhomboid-like protein (PARL) promotes changes in mitochondrial morphology
Phosphorylation and cleavage of presenilin-associated rhomboid-like protein (PARL) promotes changes in mitochondrial morphology
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DOI：
10.1073/pnas.0604983103
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发表时间：
2006-12-05
影响因子：
11.1
通讯作者：
Pellegrini, Luca
中科院分区：
文献类型：
--
作者：
Jeyaraju, Danny V.;Xu, Liqun;Pellegrini, Luca
线粒体的重塑是一个动态过程，由一组保守蛋白介导，通过细胞器内外膜的融合和分裂来协调。在后生动物中，线粒体形态学背后的分子机制已被招募来管理新的功能，如发育，钙信号和凋亡，这表明应该存在新的机制来调节保守的膜融合/分裂机制。在这里，我们表明，磷酸化和哺乳动物早老蛋白相关的菱形样（PARL）蛋白酶的脊椎动物特异性P β结构域的切割可以影响线粒体形态。嵌入该结构域的三个残基Ser-65、Thr-69和Ser-70的磷酸化损害了启动PARL诱导的线粒体片段化所需的位置Ser（77）-Ala（78）处的切割。我们的研究结果揭示了PARL磷酸化和切割影响线粒体动力学，为研究线粒体形态的分子进化提供了蓝图。
Remodeling of mitochondria is a dynamic process coordinated by fusion and fission of the inner and outer membranes of the organelle, mediated by a set of conserved proteins. In metazoans, the molecular mechanism behind mitochondrial morphology has been recruited to govern novel functions, such as development, calcium signaling, and apoptosis, which suggests that novel mechanisms should exist to regulate the conserved membrane fusion/fission machinery. Here we show that phosphorylation and cleavage of the vertebrate-specific P beta domain of the mammalian presenilin-associated rhomboid-like (PARL) protease can influence mitochondrial morphology. Phosphorylation of three residues embedded in this domain, Ser-65, Thr-69, and Ser-70, impair a cleavage at position Ser(77)-Ala(78) that is required to initiate PARL-induced mitochondrial fragmentation. Our findings reveal that PARL phosphorylation and cleavage impact mitochondria dynamics, providing a blueprint to study the molecular evolution of mitochondrial morphology.