Hax1 lacks BH modules and is peripherally associated to heavy membranes: implications for Omi/HtrA2 and PARL activity in the regulation of mitochondrial stress and apoptosis.
Hax1 lacks BH modules and is peripherally associated to heavy membranes: implications for Omi/HtrA2 and PARL activity in the regulation of mitochondrial stress and apoptosis.
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DOI：
10.1038/cdd.2009.110
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发表时间：
2009-12
影响因子：
12.4
通讯作者：
Pellegrini, L.
中科院分区：
文献类型：
--
作者：
Jeyaraju, D. V.;Cisbani, G.;De Brito, O. M.;Koonin, E. V.;Pellegrini, L.
HAX1在免疫缺陷综合征和凋亡中起重要作用。最近，Chao等人（自然，2008年）报道，HAX1是一种与Bcl-2 - 元素相关的蛋白质，通过一种机制抑制淋巴细胞和神经元中凋亡的蛋白质，该机制涉及与菱形蛋白酶在线粒体膜间空间中的菱形蛋白酶PARL（ ims）。从机械上讲，HAX1/PARL相互作用允许募集丝氨酸蛋白酶OMI/HTRA2及其对PARL的呈现，该丝氨酸蛋白酶裂解以产生一种OMI/HTRA2形式，该形式可能会在线粒体外膜透明膜透明化过程中蛋白水解消除活性BAX（MOMP）。这项研究的结果表明，控制细胞类型对促凋亡刺激的敏感性受IMS中的PAR/HAX1复合物的控制，更一般而言，BCl-2与户主相关的蛋白可以控制MOMP。线粒体。此外，它定义了一种新型的抗凋亡OPA1独立于PARL的途径。在这里，我们提供的证据表明HAX1不是与Bcl-2与户主相关的蛋白质。同样，在体内HAX1的活性不能在机械上耦合到PARL，因为两种蛋白质局限于不同的细胞室，并且它们在体外的相互作用是伪影。我们的结果表明，HAX1在细胞凋亡中的功能和机制不同，并重新开辟了一个问题：除凋亡外，是否还通过OMI/HTRA2处理来调节线粒体应激反应。
Hax1 plays an important role in immunodeficiency syndromes and apoptosis. Recently, Chao et al., (Nature, 2008) reported that Hax1 is a Bcl-2-family-related protein required to suppress apoptosis in lymphocytes and neurons via a mechanism that involves association to the rhomboid protease PARL in the mitochondria intermembrane space (IMS). Mechanistically, Hax1/PARL interaction allows the recruitment of the serine protease Omi/HtrA2 and its presentation to PARL, which cleaves it to generate a form of Omi/HtrA2 that may proteolytically eliminate active Bax during mitochondrial outer membrane permeabilization (MOMP). The results of this study imply that the control of cell-type sensitivity to proapoptotic stimuli is governed by the PARL/Hax1 complex in the IMS and, more generally, that Bcl-2-family-related proteins can control MOMP from the inside of the mitochondrion. Further, it defines a novel, antiapoptotic Opa1-independent pathway for PARL. Here we present evidence that Hax1 is not a Bcl-2-family-related protein. Also, that in vivo the activity of Hax1 cannot be mechanistically coupled to PARL because the two proteins are confined in distinct cellular compartments and their interaction in vitro is an artifact. Our results indicate a different function and mechanism of Hax1 in apoptosis and re-opens the question of whether mammalian PARL, in addition to apoptosis, regulates mitochondrial stress response through Omi/HtrA2 processing.
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影响因子：
14.9
作者：
Cole C;Barber JD;Barton GJ
通讯作者：
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影响因子：
4.8
作者：
Kasashima, Katsumi;Ohta, Eriko;Endo, Hitoshi
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影响因子：
14.8
作者：
Frezza, Christian;Cipolat, Sara;Scorrano, Luca
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影响因子：
56.9
作者：
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通讯作者：
Koonin, EV
DOI：
10.1073/pnas.0604983103
发表时间：
2006-12-05
影响因子：
11.1
作者：
Jeyaraju, Danny V.;Xu, Liqun;Pellegrini, Luca
通讯作者：
Pellegrini, Luca