Berneburg Mark, Gremmel Tobias, Kürten Viola, Schroeder Peter, Hertel Ines, von Mikecz Anna, Wild Susanne, Chen Min, Declercq Lieve, Matsui Mary, Ruzicka Thomas, Krutmann Jean
Molecular Oncology and Aging, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany.
J Invest Dermatol. 2005 Aug;125(2):213-20. doi: 10.1111/j.0022-202X.2005.23806.x.
Mutations of mitochondrial (mt) DNA play a role in neurodegeneration, normal aging, premature aging of the skin (photoaging), and tumors. We and others could demonstrate that mtDNA mutations can be induced in skin cells in vitro and in normal human skin in vivo by repetitive, sublethal ultraviolet (UV)-A-irradiation. These mutations are mediated by singlet oxygen and persist in human skin as long-term biomarkers of UV exposure. Although mtDNA exclusively encodes for the respiratory chain, involvement of the energy metabolism in mtDNA mutagenesis and a protective role of the energy precursor creatine have thus far not been shown. We assessed the amount of a marker mutation of mtDNA, the so-called common deletion, by real-time PCR. Induction of the common deletion was paralleled by a measurable decrease of oxygen consumption, mitochondrial membrane potential, and ATP content, as well as an increase of matrix metalloproteinase-1. Mitochondrial mutagenesis as well as functional consequences could be normalized by increasing intracellular creatine levels. These data indicate that increase of the energy precursor creatine protects from functionally relevant, aging-associated mutations of mitochondrial DNA.
线粒体（mt）DNA突变在神经退行性变、正常衰老、皮肤过早衰老（光老化）和肿瘤中起作用。我们和其他人已经证明，通过重复、亚致死剂量的紫外线（UV）-A照射，mtDNA突变可在体外皮肤细胞和体内正常人皮肤中被诱导。这些突变由单线态氧介导，并作为紫外线暴露的长期生物标志物存在于人类皮肤中。尽管mtDNA仅编码呼吸链，但迄今为止，能量代谢在mtDNA诱变中的作用以及能量前体肌酸的保护作用尚未得到证实。我们通过实时PCR评估了mtDNA的一种标记突变，即所谓的常见缺失的数量。常见缺失的诱导与氧消耗可测量的减少、线粒体膜电位和ATP含量的减少以及基质金属蛋白酶-1的增加同时发生。通过增加细胞内肌酸水平，线粒体诱变以及功能后果可以恢复正常。这些数据表明，能量前体肌酸的增加可保护线粒体DNA免受与功能相关的、与衰老相关的突变。
