Manev Hari, Dzitoyeva Svetlana, Chen Hu
The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA.
Biomol Concepts. 2012 Apr;3(2):107-115. doi: 10.1515/bmc-2011-0058. Epub 2012 Apr 11.
Neuroepigenetics, which includes nuclear DNA modifications such as 5-methylcytosine and 5-hydoxymethylcytosine and modifications of nuclear proteins such as histones, is emerging as the leading field in molecular neuroscience. Historically, a functional role for epigenetic mechanisms, including in neuroepigenetics, has been sought in the area of the regulation of nuclear transcription. However, one important compartment of mammalian cell DNA, different from nuclear but equally important for physiological and pathological processes (including in the brain), mitochondrial DNA has for the most part not had a systematic epigenetic characterization. The importance of mitochondria and mitochondrial DNA (particularly its mutations) in central nervous system physiology and pathology has long been recognized. Only recently have mechanisms of mitochondrial DNA methylation and hydroxymethylation, including the discovery of mitochondrial DNA-methyltransferases and the presence and the functionality of 5-methylcytosine and 5-hydroxymethylcytosine in mitochondrial DNA (e.g., in modifying the transcription of mitochondrial genome), been unequivocally recognized as a part of mammalian mitochondrial physiology. Here we summarize for the first time evidence supporting the existence of these mechanisms and we propose the term "mitochondrial epigenetics" to be used when referring to them. Currently, neuroepigenetics does not include mitochondrial epigenetics - a gap that we expect to close in the near future.
神经表观遗传学，包括核DNA修饰（如5-甲基胞嘧啶和5-羟甲基胞嘧啶）以及核蛋白修饰（如组蛋白），正成为分子神经科学的前沿领域。从历史上看，人们一直在核转录调控领域探寻表观遗传机制（包括神经表观遗传学）的功能作用。然而，哺乳动物细胞DNA的一个重要组成部分，不同于细胞核但对生理和病理过程（包括大脑中的过程）同样重要，线粒体DNA在很大程度上尚未得到系统的表观遗传学特征描述。线粒体和线粒体DNA（尤其是其突变）在中枢神经系统生理和病理中的重要性早已得到认可。直到最近，线粒体DNA甲基化和羟甲基化机制，包括线粒体DNA甲基转移酶的发现以及线粒体DNA中5-甲基胞嘧啶和5-羟甲基胞嘧啶的存在及其功能（例如，在修饰线粒体基因组转录方面），才被明确认定为哺乳动物线粒体生理学的一部分。在此，我们首次总结支持这些机制存在的证据，并提议在提及它们时使用“线粒体表观遗传学”这一术语。目前，神经表观遗传学并不包括线粒体表观遗传学——我们预计在不久的将来填补这一空白。
