Elpeleg Orly, Miller Chaya, Hershkovitz Eli, Bitner-Glindzicz Maria, Bondi-Rubinstein Gili, Rahman Shamima, Pagnamenta Alistair, Eshhar Sharon, Saada Ann
Metabolic Disease Unit, Shaare-Zedek Medical Center, Jerusalem, Israel.
Am J Hum Genet. 2005 Jun;76(6):1081-6. doi: 10.1086/430843. Epub 2005 Apr 22.
The mitochondrial DNA (mtDNA) depletion syndrome is a quantitative defect of mtDNA resulting from dysfunction of one of several nuclear-encoded factors responsible for maintenance of mitochondrial deoxyribonucleoside triphosphate (dNTP) pools or replication of mtDNA. Markedly decreased succinyl-CoA synthetase activity due to a deleterious mutation in SUCLA2, the gene encoding the beta subunit of the ADP-forming succinyl-CoA synthetase ligase, was found in muscle mitochondria of patients with encephalomyopathy and mtDNA depletion. Succinyl-CoA synthetase is invariably in a complex with mitochondrial nucleotide diphosphate kinase; hence, we propose that a defect in the last step of mitochondrial dNTP salvage is a novel cause of the mtDNA depletion syndrome.
线粒体DNA（mtDNA）耗竭综合征是一种mtDNA的定量缺陷，由负责维持线粒体脱氧核苷三磷酸（dNTP）池或mtDNA复制的几种核编码因子之一的功能障碍引起。在患有脑病和mtDNA耗竭的患者的肌肉线粒体中发现，由于编码生成ADP的琥珀酰辅酶A合成酶连接酶β亚基的基因SUCLA2发生有害突变，琥珀酰辅酶A合成酶活性显著降低。琥珀酰辅酶A合成酶总是与线粒体核苷二磷酸激酶形成复合物；因此，我们提出线粒体dNTP补救的最后一步缺陷是mtDNA耗竭综合征的一个新病因。
