Mitochondrial Phospholipase A(2) Activated by Reactive Oxygen Species in Heart Mitochondria Induces Mild Uncoupling

作者：Jezek J^*; Jaburek M; Zelenka J; Jezek P

来源：Physiological Research, 2010, 59(5): 737-747.

DOI：10.33549/physiolres.931905

• Heart mitochondrial phospholipase A(2)
• Fatty acids
• Uncoupling of mitochondria
• Adenine nucleotide translocase
• Defense against oxidative stress

Homeostasis of reactive oxygen species (ROS) in cardiomyocytes is critical for elucidation of normal heart physiology and pathology. Mitochondrial phospholipases A(2) (mt-PLA(2)) have been previously suggested to be activated by ROS. Therefore, we have attempted to elucidate physiological role of such activation. We have found that function of a specific i-isoform of mitochondrial phospholipase A(2) (mt-iPLA(2)) is activated by tert-butylhydroperoxide in isolated rat heart mitochondria. Isoform specificity was judged from the inhibition by bromoenol lactone (BEL), a specific iPLA(2) inhibitor. Concomitant uncoupling has been caused by free fatty acids, since it was inhibited by bovine serum albumin. The uncoupling was manifested as a respiration burst accompanied by a slight decrease in mitochondrial inner membrane potential. Since this uncoupling was sensitive to carboxyatractyloside and purine nucleotide di- and tri-phosphates, we conclude that it originated from the onset of fatty acid cycling mediated by the adenine nucleotide translocase (major contribution) and mitochondrial uncoupling protein(s) (minor contribution), respectively. Such a mild uncoupling may provide a feedback downregulation of oxidative stress, since it can further attenuate mitochondrial production of ROS. In conclusion, ROS-induced function of cardiac mt-iPLA(2) may stand on a pro-survival side of ischemia-reperfusion injury.

• 出版日期2010