Mitochondrial nucleic acid binding proteins associated with diseases.
Mitochondrial nucleic acid binding proteins associated with diseases.
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DOI：
10.2741/4479
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
T. Uchiumi;D. Kang
中科院分区：
文献类型：
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作者：
T. Uchiumi;D. Kang
哺乳动物线粒体DNA（mtDNA）存在于称为类核的结构中，其对应于核DNA的构型。线粒体转录因子A（TFAM）是一种线粒体DNA转录因子，对线粒体DNA的包装和维持起着重要作用。为了研究TFAM的功能方面，我们鉴定了许多RNA结合蛋白作为候选TFAM相互作用物，包括ERAL 1和p32。在这篇综述中，我们首先描述TFAM，复制蛋白，如聚合酶γ和Twinkle，和线粒体RNA结合蛋白的功能。我们描述了线粒体核酸结合蛋白在线粒体基质中的作用和两个线粒体膜间隙内的氧化磷酸化相关蛋白。然后，我们讨论了线粒体功能障碍是如何与几种疾病，包括线粒体呼吸系统疾病，米勒综合征和癌症。我们还描述了p32基因敲除小鼠，这是胚胎致死，并表现出呼吸链缺陷。米勒综合征是一种隐性疾病，其特征是轴后肢面骨发育不全，由DHODH突变引起。最后，我们解释了p32和线粒体肌酸激酶可能是前列腺癌进展的新标志物。
Mammalian mitochondrial DNA (mtDNA) exists in structures called nucleoids, which correspond to the configuration of nuclear DNA. Mitochondrial transcription factor A (TFAM), first cloned as an mtDNA transcription factor, is critical for packaging and maintaining mtDNA. To investigate functional aspects of TFAM, we identified many RNA-binding proteins as candidate TFAM interactors, including ERAL1 and p32. In this review, we first describe the functions of TFAM, replication proteins such as polymerase gamma and Twinkle, and mitochondrial RNA binding proteins. We describe the role of mitochondrial nucleic acid binding proteins within the mitochondrial matrix and two oxidative phosphorylation-related proteins within the mitochondrial intermembrane space. We then discuss how mitochondrial dysfunction is related to several diseases, including mitochondrial respiratory disease, Miller syndrome and cancer. We also describe p32 knockout mice, which are embryonic lethal and exhibit respiratory chain defects. Miller syndrome is a recessive disorder characterized by postaxial acrofacial dysostosis and caused by a mutation in DHODH. Finally, we explain that p32 and mitochondrial creatine kinase may be novel markers for the progression of prostate cancer.