Animals require an immediate response to oxygen availability to allow rapid shifts between oxidative and glycolytic metabolism. These metabolic shifts are highly regulated by the HIF transcription factor. The factor inhibiting HIF (FIH) is an asparaginyl hydroxylase that controls HIF transcriptional activity in an oxygen-dependent manner. We show here that FIH loss increases oxidative metabolism, while also increasing glycolytic capacity, and that this gives rise to an increase in oxygen consumption. We further show that the loss of FIH acts to accelerate the cellular metabolic response to hypoxia. Skeletal muscle expresses 50-fold higher levels of FIH than other tissues: we analyzed skeletal muscle FIH mutants and found a decreased metabolic efficiency, correlated with an increased oxidative rate and an increased rate of hypoxic response. We find that FIH, through its regulation of oxidation, acts in concert with the PHD/vHL pathway to accelerate HIF-mediated metabolic responses to hypoxia.

中文翻译：

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抑制HIF天冬酰胺基羟化酶的因子可调节氧化代谢，并加速对缺氧的代谢适应。

动物需要立即对氧气供应作出反应，以使氧化和糖酵解代谢之间快速转换。这些代谢变化受到HIF转录因子的高度调控。抑制HIF（FIH）的因子是一种以氧依赖性方式控制HIF转录活性的天冬酰胺基羟化酶。我们在这里表明，FIH损失增加了氧化代谢，同时也增加了糖酵解能力，并且这导致了氧气消耗的增加。我们进一步表明，FIH的丧失可促进细胞对缺氧的代谢反应。骨骼肌表达的FIH比其他组织高50倍：我们分析了骨骼肌FIH突变体，发现其代谢效率降低，与氧化率增加和缺氧反应率增加相关。