美国哈佛医学院Marcia C. Haigis研究组宣布他们发现脯氨酰羟化酶3（PHD3）缺失增强骨骼肌的运动能力和脂肪氧化。相关论文于2020年7月13日在线发表于《细胞-代谢》杂志。

研究人员发现乙酰辅酶A羧化酶2（ACC2）磷酸化和羟基化以相反的方式发生。在高耗能条件下ACC2发生羟基化，并抑制脂肪酸氧化。PHD3缺失的小鼠表现出心脏和骨骼肌中ACC2羟基化丢失，并且脂肪酸氧化加剧。在耐力运动挑战中，全身或骨骼肌特定PHD3缺失的小鼠其运动能力增强。总之，这些数据揭示了AMPK和PHD3之间的关联，以及PHD3在急性运动耐力和骨骼肌代谢中的作用。

据了解，细胞新陈代谢的快速变化使组织在能量利用变化期间维持体内平衡。核心代谢调节剂ACC2在细胞能量应激期间被AMP激活的蛋白激酶（AMPK）磷酸化，以减轻其对脂肪氧化的抑制作用。虽然ACC2也可以被PHD3羟基化，但是其造成的生理影响却鲜为人知。

附：英文原文

Title: PHD3 Loss Promotes Exercise Capacity and Fat Oxidation in Skeletal Muscle

Author: Haejin Yoon, Jessica B. Spinelli, Elma Zaganjor, Samantha J. Wong, Natalie J. German, Elizabeth C. Randall, Afsah Dean, Allen Clermont, Joao A. Paulo, Daniel Garcia, Hao Li, Olivia Rombold, Nathalie Y.R. Agar, Laurie J. Goodyear, Reuben J. Shaw, Steven P. Gygi, Johan Auwerx, Marcia C. Haigis

Issue&Volume: 2020-07-13

Abstract: Rapid alterations in cellular metabolism allow tissues to maintain homeostasis duringchanges in energy availability. The central metabolic regulator acetyl-CoA carboxylase2 (ACC2) is robustly phosphorylated during cellular energy stress by AMP-activatedprotein kinase (AMPK) to relieve its suppression of fat oxidation. While ACC2 canalso be hydroxylated by prolyl hydroxylase 3 (PHD3), the physiological consequencethereof is poorly understood. We find that ACC2 phosphorylation and hydroxylationoccur in an inverse fashion. ACC2 hydroxylation occurs in conditions of high energyand represses fatty acid oxidation. PHD3-null mice demonstrate loss of ACC2 hydroxylationin heart and skeletal muscle and display elevated fatty acid oxidation. Whole bodyor skeletal muscle-specific PHD3 loss enhances exercise capacity during an enduranceexercise challenge. In sum, these data identify an unexpected link between AMPK andPHD3, and a role for PHD3 in acute exercise endurance capacity and skeletal musclemetabolism.

DOI: 10.1016/j.cmet.2020.06.017

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30318-1