Inactivation of Pill helicase causes a mitochondrial myopathy in mice
Inactivation of Pill helicase causes a mitochondrial myopathy in mice
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DOI：
10.1016/j.mito.2016.02.005
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发表时间：
2016-09-01
期刊：
影响因子：
4.4
通讯作者：
Paquis-Flucklinger, Veronique
中科院分区：
文献类型：
--
作者：
Bannwarth, Sylvie;Berg-Alonso, Laetitia;Paquis-Flucklinger, Veronique
编码线粒体解旋酶（如TWINKLE和DNA 2）的基因中的突变涉及人和小鼠中具有mtDNA不稳定性的线粒体肌病。我们发现，线粒体解旋酶家族的第三个成员Pti 1的失活，在小鼠中引起类似的表型。PIF 1-/-动物发展为具有呼吸链缺陷的线粒体肌病。Pif 1失活导致小鼠胚胎成纤维细胞中氧化应激诱导的mtDNA损伤修复缺陷，通过与线粒体同种型mPif 1互补可以改善这种缺陷（67）。这些结果为mtDNA不稳定性疾病患者的探索开辟了新的视角。(C)2016 Elsevier B. V.和线粒体研究学会。All rights reserved.
Mutations in genes coding for mitochondrial helicases such as TWINKLE and DNA2 are involved in mitochondrial myopathies with mtDNA instability in both human and mouse. We show that inactivation of Pti1, a third member of the mitochondrial helicase family, causes a similar phenotype in mouse. pif1 -/- animals develop a mitochondria] myopathy with respiratory chain deficiency. Pif1 inactivation is responsible for a deficiency to repair oxidative stress-induced mtDNA damage in mouse embryonic fibroblasts that is improved by complementation with mitochondrial isoform mPif1(67). These results open new perspectives for the exploration of patients with mtDNA instability disorders. (C) 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.