MRC Mitochondrial Biology Unit, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK; Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0QQ, UK.
MRC Mitochondrial Biology Unit, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK; Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0QQ, UK.
Trends Endocrinol Metab. 2018 Apr;29(4):249-259. doi: 10.1016/j.tem.2018.02.002. Epub 2018 Feb 28.
Alterations in mitochondrial metabolism influence cell differentiation and growth. This process is regulated by the activity of 2-oxoglutarate (2OG)-dependent dioxygenases (2OGDDs) - a diverse superfamily of oxygen-consuming enzymes - through modulation of the epigenetic landscape and transcriptional responses. Recent reports have described the role of mitochondrial metabolites in directing 2OGDD-driven cell-fate switches in stem cells (SCs), immune cells, and cancer cells. An understanding of the metabolic mechanisms underlying 2OGDD autoregulation is required for therapeutic targeting of this system. We propose a model dependent on oxygen and metabolite availability and discuss how this integrates 2OGDD metabolic signalling, the hypoxic transcriptional response, and fate-determining epigenetic changes.
线粒体代谢的改变会影响细胞的分化和生长。这个过程受到 2-氧戊二酸（2OG）依赖性双加氧酶（2OGDD）的活性调控，2OGDD 是一个具有广泛多样性的耗氧酶超家族，通过调节表观遗传景观和转录反应来实现。最近的报告描述了线粒体代谢物在指导干细胞（SCs）、免疫细胞和癌细胞中 2OGDD 驱动的细胞命运转变中的作用。为了对该系统进行治疗性靶向，了解 2OGDD 自身调控的代谢机制是必要的。我们提出了一个依赖于氧和代谢物可用性的模型，并讨论了它如何整合 2OGDD 代谢信号、缺氧转录反应和决定命运的表观遗传变化。
