期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 91, 期 -, 页码 63-71出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2015.10.036
关键词
Cyclophilin D; Mitochondrial flash; Metabolism; Heart; Skeletal muscle
资金
- National Key Basic Research Program of China [2013CB531200]
- National Natural Science Foundation of China [31371350, 31130067, 31221002, 31327901]
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.
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