Kang Dongchon, Kim Sang Ho, Hamasaki Naotaka
Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Mitochondrion. 2007 Feb-Apr;7(1-2):39-44. doi: 10.1016/j.mito.2006.11.017. Epub 2006 Dec 8.
A growing body of evidence suggests that mammalian mitochondrial DNA takes on higher structure called nucleoid or mitochromosome corresponding to that of nuclear DNA. Mitochondrial transcription factor A (TFAM), which was cloned as a transcription factor for mitochondrial DNA, has known to be essential for the maintenance of mitochondrial DNA. Human TFAM has an ability to bind to DNA in a sequence-independent manner and is abundant enough to cover whole region of mitochondrial DNA, owing to which TFAM stabilizes mitochondrial DNA through formation of nucleoid and regulates (or titrates) the amount of mitochondrial DNA. Overexpression of human TFAM in mice increases the amount of mitochondrial DNA and dramatically ameliorates the cardiac dysfunctions caused by myocardial infarction. The maintenance of integrity of mitochondrial DNA is important for keeping proper cellular functions both under physiological and pathological conditions. TFAM may play a crucial role in maintaining mitochondrial DNA as a main component of the nucleoid.
越来越多的证据表明，哺乳动物的线粒体DNA呈现出一种更高层次的结构，称为类核或线粒体染色体，与核DNA的结构相对应。线粒体转录因子A（TFAM）最初作为线粒体DNA的转录因子被克隆出来，已知它对于线粒体DNA的维持至关重要。人类TFAM具有以序列非依赖方式结合DNA的能力，并且其含量丰富，足以覆盖线粒体DNA的整个区域，因此TFAM通过形成类核来稳定线粒体DNA，并调节（或滴定）线粒体DNA的数量。在小鼠中过表达人类TFAM会增加线粒体DNA的数量，并显著改善由心肌梗死引起的心脏功能障碍。在生理和病理条件下，维持线粒体DNA的完整性对于保持适当的细胞功能都很重要。TFAM作为类核的主要成分，可能在维持线粒体DNA方面发挥关键作用。
