A specific isoform of poly(ADP-ribose) glycohydrolase is targeted to the mitochondrial matrix by a N-terminal mitochondrial targeting sequence.
A specific isoform of poly(ADP-ribose) glycohydrolase is targeted to the mitochondrial matrix by a N-terminal mitochondrial targeting sequence.
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聚（ADP-核糖）糖水解酶的特定亚型通过 N 端线粒体靶向序列靶向线粒体基质。
DOI：
10.1016/j.yexcr.2009.04.005
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发表时间：
2009
影响因子：
3.7
通讯作者：
Jacobson,MyronK
中科院分区：
文献类型：
--
作者：
Whatcott,CliffordJ;Meyer-Ficca,MirellaL;Meyer,RalphG;Jacobson,MyronK
聚（ADP-核糖）聚合酶（PARP）将NAD转化为ADP-核糖聚合物，所述ADP-核糖聚合物通过聚（ADP-核糖）糖水解酶（PARG）转化为游离ADP-核糖。基因毒性应激后核酶PARP-1的激活与线粒体释放凋亡诱导因子有关，但信号在核和线粒体区室之间传递的机制尚不清楚。本文报道的研究检查了PARG与HeLa细胞线粒体之间的关系。与线粒体组分相关的内源性PARG在60 kDa的范围内迁移。如通过全细胞的亚细胞分级分离和免疫荧光显微镜所证明的，用在N-末端具有由外显子4编码的氨基酸的PARG表达构建体瞬时转染细胞靶向线粒体。缺失和错义突变体允许鉴定由PARG外显子4编码的前16个氨基酸组成的典型N-末端线粒体靶向序列。亚线粒体定位实验表明，这种线粒体PARG亚型靶向线粒体基质。PARG亚型作为线粒体基质的一个组成部分的鉴定提出了几个有趣的可能性，涉及细胞死亡途径的调节的核-线粒体串扰的机制。
Poly(ADP-ribose) polymerases (PARPs) convert NAD to polymers of ADP-ribose that are converted to free ADP-ribose by poly(ADP-ribose) glycohydrolase (PARG). The activation of the nuclear enzyme PARP-1 following genotoxic stress has been linked to release of apoptosis inducing factor from the mitochondria, but the mechanisms by which signals are transmitted between nuclear and mitochondrial compartments are not well understood. The study reported here has examined the relationship between PARG and mitochondria in HeLa cells. Endogenous PARG associated with the mitochondrial fraction migrated in the range of 60 kDa. Transient transfection of cells with PARG expression constructs with amino acids encoded by exon 4 at the N-terminus was targeted to the mitochondria as demonstrated by subcellular fractionation and immunofluorescence microscopy of whole cells. Deletion and missense mutants allowed identification of a canonical N-terminal mitochondrial targeting sequence consisting of the first 16 amino acids encoded by PARG exon 4. Sub-mitochondrial localization experiments indicate that this mitochondrial PARG isoform is targeted to the mitochondrial matrix. The identification of a PARG isoform as a component of the mitochondrial matrix raises several interesting possibilities concerning mechanisms of nuclear-mitochondrial cross talk involved in regulation of cell death pathways.