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.

中文翻译：

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线粒体和缺氧：细胞命运决定中的代谢串扰

线粒体代谢的改变影响细胞分化和生长。该过程受 2-酮戊二酸 (2OG) 依赖性双加氧酶 (2OGDD) 的活性调节 - 一个多样化的耗氧酶超家族 - 通过调节表观遗传景观和转录反应。最近的报告描述了线粒体代谢物在指导干细胞 (SC)、免疫细胞和癌细胞中 2OGDD 驱动的细胞命运转换中的作用。该系统的治疗靶向需要了解 2OGDD 自动调节基础的代谢机制。我们提出了一个依赖于氧气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。