Cells cope with environmental changes through various mechanisms. Pathways involving HIF-1, SIRT1, and AMPK play major roles in energy homeostasis under stress conditions. Diacylglycerol kinase (DGK) constitutes an enzyme family that catalyzes conversion of diacylglycerol to phosphatidic acid. We reported earlier that energy depletion such as ischemia induces proteasomal degradation of DGKζ before cell death, suggesting involvement of DGKζ in energy homeostasis. This study examines how DGKζ depletion affects the regulation of HIF-1α, SIRT1, and AMPKα. Under hypoxia DGKζ depletion attenuates HIF-1α induction and SIRT1 expression, which might render cells vulnerable to energy stress. However, DGKζ depletion engenders enhanced AMPKα phosphorylation by upstream kinase TAK1 and an increase in intracellular ATP levels. Results suggest that DGKζ exerts a suppressive effect on TAK1 activity in the AMPK activation mechanism, and that DGKζ depletion might engender dysregulation of the AMPK-mediated energy sensor system.

中文翻译：

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DGKζ 耗竭减弱了 HIF-1α 诱导和 SIRT1 表达，但增强了缺氧条件下 TAK1 介导的 AMPKα 磷酸化。

细胞通过各种机制应对环境变化。涉及 HIF-1、SIRT1 和 AMPK 的通路在压力条件下的能量稳态中起主要作用。二酰基甘油激酶 (DGK) 构成一个酶家族，可催化​​二酰基甘油转化为磷脂酸。我们之前报道过能量消耗如缺血会在细胞死亡前诱导 DGKζ 的蛋白酶体降解，表明 DGKζ 参与能量稳态。本研究探讨了 DGKζ 耗竭如何影响 HIF-1α、SIRT1 和 AMPKα 的调节。在缺氧条件下，DGKζ 耗竭减弱了 HIF-1α 诱导和 SIRT1 表达，这可能使细胞容易受到能量压力的影响。然而，DGKζ 耗竭导致上游激酶 TAK1 增强 AMPKα 磷酸化并增加细胞内 ATP 水平。