Background

Virtually all eukaryotic cells contain spatially distinct genomes, a single nuclear genome that harbours the vast majority of genes and much smaller genomes found in mitochondria present at thousands of copies per cell. To generate a coordinated gene response to various environmental cues, the genomes must communicate with each another. Much of this bi-directional crosstalk relies on epigenetic processes, including DNA, RNA, and histone modification pathways. Crucially, these pathways, in turn depend on many metabolites generated in specific pools throughout the cell, including the mitochondria. They also involve the transport of metabolites as well as the enzymes that catalyse these modifications between nuclear and mitochondrial genomes.

Scope of review

This study examines some of the molecular mechanisms by which metabolites influence the activity of epigenetic enzymes, ultimately affecting gene regulation in response to metabolic cues. We particularly focus on the subcellular localisation of metabolite pools and the crosstalk between mitochondrial and nuclear proteins and RNAs. We consider aspects of mitochondrial-nuclear communication involving histone proteins, and potentially their epigenetic marks, and discuss how nuclear-encoded enzymes regulate mitochondrial function through epitranscriptomic pathways involving various classes of RNA molecules within mitochondria.

Major conclusions

Epigenetic communication between nuclear and mitochondrial genomes occurs at multiple levels, ultimately ensuring a coordinated gene expression response between different genetic environments. Metabolic changes stimulated, for example, by environmental factors, such as diet or physical activity, alter the relative abundances of various metabolites, thereby directly affecting the epigenetic machinery. These pathways, coupled to regulated protein and RNA transport mechanisms, underpin the coordinated gene expression response. Their overall importance to the fitness of a cell is highlighted by the identification of many mutations in the pathways we discuss that have been linked to human disease including cancer.

中文翻译：

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两个基因组，一个细胞：通过表观遗传途径的线粒体-核配位。

背景

几乎所有的真核细胞都在空间上具有不同的基因组，一个核基因组具有绝大多数基因，而线粒体中存在的基因组要小得多，每个细胞存在数千个拷贝。为了对各种环境线索产生协调一致的基因响应，基因组必须彼此通信。这种双向串扰在很大程度上取决于表观遗传过程，包括DNA，RNA和组蛋白修饰途径。至关重要的是，这些途径又取决于整个细胞（包括线粒体）特定池中产生的许多代谢产物。它们还涉及代谢物的运输以及催化核和线粒体基因组之间这些修饰的酶。

审查范围

这项研究检查了代谢产物影响表观遗传酶活性的分子机制，最终影响了对代谢线索的基因调控。我们特别关注代谢物池的亚细胞定位以及线粒体与核蛋白和RNA之间的串扰。我们考虑了涉及组蛋白的线粒体-核通讯方面，并可能考虑了它们的表观遗传标记，并讨论了核编码酶如何通过涉及线粒体内各种RNA分子的转录组途径调节线粒体功能。

主要结论

核和线粒体基因组之间的表观遗传学交流发生在多个层面，最终确保了不同遗传环境之间协调的基因表达响应。例如，环境因素（如饮食或体育锻炼）刺激的代谢变化会改变各种代谢产物的相对丰度，从而直接影响表观遗传机制。这些途径，再加上调节的蛋白质和RNA转运机制，支撑了协调的基因表达反应。在我们讨论的途径中许多与人类疾病（包括癌症）相关的突变的鉴定，突显了它们对细胞适应性的总体重要性。