Pathogenic mitochondrial DNA-induced respiration defects in hematopoietic cells result in anemia by suppressing erythroid differentiation
Pathogenic mitochondrial DNA-induced respiration defects in hematopoietic cells result in anemia by suppressing erythroid differentiation
复制标题
DOI：
10.1016/j.febslet.2007.03.092
复制
发表时间：
2007-05-01
期刊：
影响因子：
3.5
通讯作者：
Hayashi, Jun-Ichi
中科院分区：
文献类型：
--
作者：
Inoue, Shin-Ichi;Yokota, Mutsumi;Hayashi, Jun-Ichi
贫血是皮尔逊综合征患者的一种症状，由突变的线粒体DNA（mtDNA）积累引起。这种突变的mtDNA已在贫血患者中检测到。这表明，线粒体DNA突变导致的呼吸缺陷是贫血的原因。然而，目前还没有令人信服的实验证据来证实造血细胞呼吸缺陷与贫血表达之间的病理生理关系。我们通过将携带大规模缺失的致病性mtDNA（Delta mtDNA）的骨髓细胞移植到正常小鼠中来解决这个问题。骨髓移植小鼠仅在造血细胞中携带高比例的Delta mtDNA，导致小鼠发生大红细胞性贫血。他们表现出异常的红细胞分化和弱红细胞生成反应的压力条件。这些观察结果表明，造血细胞特异性呼吸缺陷引起的mtDNA致病突变是负责贫血诱导异常红细胞生成。(c)2007年欧洲生物化学学会联合会。Elsevier B.V.出版，保留所有权利。
Anemia is a symptom in patients with Pearson syndrome caused by the accumulation of mutated mitochondrial DNA (mtDNA). Such mutated mtDNAs have been detected in patients with anemia. This suggested that respiration defects due to mutated mtDNA are responsible for the anemia. However, there has been no convincing experimental evidence to confirm the pathophysiological relation between respiration defects in hematopoietic cells and expression of anemia. We address this issue by transplanting bone marrow cells carrying pathogenic mtDNA with a large-scale deletion (Delta mtDNA) into normal mice. The bone marrow-transplanted mice carried high proportion of Delta mtDNA only in hematopoietic cells, and resultant the mice suffered from macrocytic anemia. They show abnormalities of erythroid differentiation and weak erythropoietic response to a stressful condition. These observations suggest that hematopoietic cell-specific respiration defects caused by mtDNAs with pathogenic mutations are responsible for anemia by inducing abnormalities in erythropoiesis. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.