Mitochondrial binding of alpha-enolase stabilizes mitochondrial membrane: Its role in doxorubicin-induced cardiomyocyte apoptosis

作者：Gao Si; Li Hong; Cai Yi; Ye Jian tao; Liu Zhi ping; Lu Jing; Huang Xiao yang; Feng Xiao jun; Gao Hui; Chen Shao rui; Li Min^*; Liu Pei qing

来源：Archives of Biochemistry and Biophysics, 2014, 542: 46-55.

DOI：10.1016/j.abb.2013.12.008

• alpha-Enolase
• Cardiomyocytes
• Apoptosis
• Mitochondria
• Doxorubicin
• Voltage dependent anion channel

alpha-Enolase is a metabolic enzyme in the catabolic glycolytic pathway. In eukaryotic cells, the subcellular compartmentalization of alpha-enolase as well as its multifaceted functions has been identified. Here, we report that alpha-enolase is a regulator of cardiac mitochondria; it partially located in the mitochondria of rat cardiomyocytes. Doxorubicin treatment displaced alpha-enolase from mitochondria, accompanied by activation of mitochondria( cell death pathway. Furthermore, in isolated mitochondria, recombinant ccenolase significantly alleviated Ca2+-induced loss of membrane potential, swelling of matrix and permeabilization of membrane. In contrast, mitochondria from alpha-enolase knockdown H9c2 myoblasts underwent more severe membrane depolarization and swelling after Ca2+ stimulation. In addition, alpha-enolase was further identified to interact with voltage dependent anion channel 1 in the outer membrane of mitochondria, which was weakened by doxorubicin. Collectively, the present study indicates that mitochondria-located alpha-enolase has a beneficial role in stabilizing mitochondrial membrane. In cardiomyocytes, the displacement of alpha-enolase from mitochondria by doxorubicin may involve in activation of the intrinsic cell death pathway.

• 单位
  广州医学院