Mitochondrial phospholipase A2 activated by reactive oxygen species in heart mitochondria induces mild uncoupling.
Homeostasis of reactive oxygen species (ROS) in cardiomyocytes is critical for elucidation of normal heart physiology and pathology. Mitochondrial phospholipases A2 (mt-PLA2) 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 A2 (mt-iPLA2) is activated by tert-butylhydroperoxide in isolated rat heart mitochondria. Isoform specificity was judged from the inhibition by bromoenol lactone (BEL), a specific iPLA2 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-iPLA2 may stand on a pro-survival side of ischemia-reperfusion injury.
Ježek
J
J
Department of Membrane Transport Biophysics, No. 75, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Jabůrek
M
M
Zelenka
J
J
Ježek
P
P
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D025461:Feedback, Physiological / Q000502:physiology; D054522:Group VI Phospholipases A2 / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000071256:Uncoupling Protein 1; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D005227:Fatty Acids; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D000071256:Uncoupling Protein 1; D000226:Mitochondrial ADP, ATP Translocases; D020122:tert-Butylhydroperoxide; D054522:Group VI Phospholipases A2; C535117:Pla2g6 protein, rat