Cyclophilin D regulates mitochondrial flashes and metabolism in cardiac myocytes
Cyclophilin D regulates mitochondrial flashes and metabolism in cardiac myocytes
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亲环蛋白 D 调节心肌细胞线粒体闪烁和代谢
DOI：
10.1016/j.yjmcc.2015.10.036
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发表时间：
2016-02-01
影响因子：
5
通讯作者：
Zheng, Ming
中科院分区：
文献类型：
--
作者：
Shang, Wei;Gao, Han;Zheng, Ming
亲环蛋白D （Cyclophilin D, CyP-D）是进化上保守的亲环蛋白家族的线粒体特异性成员，在胁迫下线粒体通透性转变（mitochondrial permeability transition， MPT）的调控中起重要作用。最近，我们已经证明，呼吸线粒体经历线粒体闪光（“mitoflash”）活动，这与生理条件下的短暂MPT相结合。然而，cypd是否以及如何调节有丝分裂仍不完全清楚。通过使用分离的心肌细胞、跳动的心脏和活小鼠骨骼肌的功能丧失和功能获得方法，我们重新审视了CyP-D在丝裂闪烁调节中的作用。cypd过表达增加，敲除减半，心脏有丝分裂频率，而有丝分裂振幅和动力学未受影响。然而，在腓肠肌中，CyP-D消融并没有改变丝裂闪频率，但丝裂闪振幅增加。这种差异伴随着小鼠心肌中cypd的表达比骨骼肌高4倍。无cyp - d心肌细胞线粒体最大呼吸速率和储备容量降低。这些数据表明，CyP-D是心脏线粒体闪光点燃和线粒体代谢的重要调节因子。此外，组织特异性的CyP-D表达可能部分解释了两种类型横纹肌中有丝闪的差异调节。(C) 2015 Elsevier Ltd.版权所有。
Cyclophilin D (CyP-D) is the mitochondrial-specific member of the evolutionally conserved cyclophilin family, and plays an important role in the regulation of mitochondrial permeability transition (MPT) under stress. Recently we have demonstrated that respiratory mitochondria undergo mitochondrial flash ("mitoflash") activity which is coupled with transient MPT under physiological conditions. However, whether and how CyP-D regulates mitoflashes remain incompletely understood. By using both loss- and gain-of-function approaches in isolated cardiomyocytes, beating hearts, and skeletal muscles in living mice, we revisited the role of CyP-D in the regulation of mitoflashes. Overexpression of CyP-D increased, and knockout of it halved, cardiac mitoflash frequency, while mitoflash amplitude and kinetics remained unaffected. However, CyP-D ablation did not alter mitoflash frequency, with mitoflash amplitude increased, in gastrocnemius muscles. This disparity was accompanied by 4-fold higher CyP-D expression in mouse cardiac than skeletal muscles. The mitochondrial maximal respiration rate and reserved capacity were reduced in CyP-D-null cardiomyocytes. These data indicate that CyP-D is a significant regulator of mitoflash ignition and mitochondrial metabolism in heart. In addition, tissue-specific CyP-D expression may partly explain the differential regulation of mitoflashes in the two types of striated muscles. (C) 2015 Elsevier Ltd. All rights reserved.