Mitochondrial phosphate-carrier deficiency:: A novel disorder of oxidative phosphorylation
Mitochondrial phosphate-carrier deficiency:: A novel disorder of oxidative phosphorylation
复制标题
DOI：
10.1086/511788
复制
发表时间：
2007-03-01
影响因子：
9.8
通讯作者：
Sperl, Wolfgang
中科院分区：
文献类型：
--
作者：
Mayr, Johannes A.;Merkel, Olaf;Sperl, Wolfgang
线粒体磷酸盐载体SLC25A3将无机磷酸盐转运到线粒体基质中，这对有氧合成三磷酸腺苷（ATP）至关重要。我们在两名患有乳酸酸中毒、肥厚性心肌病和肌肉张力减退且在出生后第一年内死亡的兄弟姐妹中，发现了该酶的选择性剪接外显子3A上的一个纯合突变 - c.215G -> A（p.Gly72Glu）。对完整线粒体的功能研究表明，肌肉中ATP合成存在缺陷，但在成纤维细胞中没有，这与肌肉中外显子3A和成纤维细胞中外显子3B的组织特异性表达相关。通过在酵母中的互补分析证实了该酶缺陷。这是关于线粒体磷酸盐载体缺陷患者的首次报道。
The mitochondrial phosphate carrier SLC25A3 transports inorganic phosphate into the mitochondrial matrix, which is essential for the aerobic synthesis of adenosine triphosphate (ATP). We identified a homozygous mutation -c.215G -> A (p.Gly72Glu)-in the alternatively spliced exon 3A of this enzyme in two siblings with lactic acidosis, hypertrophic cardiomyopathy, and muscular hypotonia who died within the 1st year of life. Functional investigation of intact mitochondria showed a deficiency of ATP synthesis in muscle but not in fibroblasts, which correlated with the tissue-specific expression of exon 3A in muscle versus exon 3B in fibroblasts. The enzyme defect was confirmed by complementation analysis in yeast. This is the first report of patients with mitochondrial phosphate-carrier deficiency.