Mitochondria and AMP-activated Protein Kinase-dependent Mechanism of Efferocytosis
Mitochondria and AMP-activated Protein Kinase-dependent Mechanism of Efferocytosis
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DOI：
10.1074/jbc.m113.489468
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发表时间：
2013-09-06
影响因子：
4.8
通讯作者：
Zmijewski, Jaroslaw W.
中科院分区：
文献类型：
--
作者：
Jiang, Shaoning;Park, Dae Won;Zmijewski, Jaroslaw W.
凋亡细胞的清除缺陷通常与炎症状态的持续有关。我们的研究结果表明，AMP激活激酶（AMPK）在巨噬细胞暴露于凋亡细胞或溶血磷脂酰胆碱，一种特定的磷脂，产生和释放的垂死细胞后，迅速激活。AMPK的激活是通过抑制线粒体耗氧量和ATP的产生来实现的，并进一步依赖于Ca 2+动员和线粒体活性氧的产生。一旦激活，AMPK增加微管合成和化学运动，并在跟踪和吞噬过程中适应能量需求。接受溶血磷脂酰胆碱的小鼠肺中凋亡细胞的摄取增加。此外，抑制AMPK会减少体外和地塞米松处理小鼠中凋亡胸腺细胞的清除。两者合计，我们得出结论，线粒体AMPK轴是一个传感器和增强剂的跟踪和清除凋亡细胞，过程中至关重要的决议炎症条件和恢复组织稳态。
Defective clearance of apoptotic cells is frequently associated with perpetuation of inflammatory conditions. Our results show a rapid activation of AMP-activated kinase (AMPK) in macrophages upon exposure to apoptotic cells or lysophosphatidylcholine, a specific phospholipid that is produced and released from dying cells. AMPK activation resulted from inhibition of mitochondrial oxygen consumption and ATP production and further depended on Ca2+ mobilization and mitochondrial reactive oxygen species generation. Once activated, AMPK increased microtubule synthesis and chemokinesis and provided adaptation to energy demand during tracking and engulfment. Uptake of apoptotic cells was increased in lungs of mice that received lysophosphatidylcholine. Furthermore, inhibition of AMPK diminished clearance of apoptotic thymocytes in vitro and in dexamethasone-treated mice. Taken together, we conclude that the mitochondrial AMPK axis is a sensor and enhancer of tracking and removal of apoptotic cell, processes crucial to resolution of inflammatory conditions and a return to tissue homeostasis.