title: Regulation of the Ca(2+)-independent phospholipase A2 in liver mitochondria by changes in the energetic state.
abstract: The effect of electron transport chain redox status on activity of the mitochondrial Ca(2+)-independent phospholipase A2 (iPLA2) has been examined. When oxidizing NAD-linked substrates, the enzyme is not active unless deenergization occurs. Uncoupler, rotenone, antimycin A, and cyanide are equally effective at upregulating the enzyme, while oligomycin is ineffective. Thenoyltrifluoroacetone causes deenergization and activates the enzyme, but only if succinate is the respiratory substrate. These findings show that the mitochondrial iPLA2 responds to the energetic state overall, rather than to the redox status of individual electron transport chain complexes. With NAD-linked substrates, and using rotenone to deenergize, iPLA2 activation can be reversed by adding succinate to reestablish a membrane potential. For this purpose, ascorbate plus N,N,N'N'-tetramethyl-phenylenediamine can be used instead of succinate and is equally effective. With succinate as substrate, the membrane potential can be reduced in a graded and stable fashion by adding increasing concentrations of malonate, which is a competitive inhibitor of succinate utilization. A partial and stable activation of the iPLA2 accompanies partial deenergization. These findings suggest that in addition to the several functions that have been proposed, the mitochondrial iPLA2 may help to coordinate local capillary blood flow with changing energy demands.
authors.affiliation: Departments of Molecular and Cellular Biochemistry Ohio State University, Columbus, OH 43210.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Rauckhorst
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Broekemeier
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Pfeiffer
mesh_terms: D000818:Animals; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D054512:Phospholipases A2, Calcium-Independent / Q000378:metabolism*; D011753:Pyrones / Q000494:pharmacology; D051381:Rats
chemical_list: D009281:Naphthalenes; D011753:Pyrones; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D054512:Phospholipases A2, Calcium-Independent
keywords: electron transport chain inhibitors; membrane potential; redox status