Regulation of the Ca2-independent phospholipase A2 in liver mitochondria by changes in the energetic state
The effect of electron transport chain redox status on activity of the mitochondrial Ca2+-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 eff...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-05-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520375027 |
| _version_ | 1818732544230686720 |
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| author | Adam J. Rauckhorst Kimberly M. Broekemeier Douglas R. Pfeiffer |
| author_facet | Adam J. Rauckhorst Kimberly M. Broekemeier Douglas R. Pfeiffer |
| author_sort | Adam J. Rauckhorst |
| collection | DOAJ |
| description | The effect of electron transport chain redox status on activity of the mitochondrial Ca2+-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. |
| first_indexed | 2024-12-17T23:35:15Z |
| format | Article |
| id | doaj.art-c9798ea61e0a4ee089d11459feb39eab |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T23:35:15Z |
| publishDate | 2014-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-c9798ea61e0a4ee089d11459feb39eab2022-12-21T21:28:35ZengElsevierJournal of Lipid Research0022-22752014-05-01555826836Regulation of the Ca2-independent phospholipase A2 in liver mitochondria by changes in the energetic stateAdam J. Rauckhorst0Kimberly M. Broekemeier1Douglas R. Pfeiffer2Departments of Molecular and Cellular Biochemistry Ohio State University, Columbus, OH 43210Institute for Mitochondrial Biology, Ohio State University, Columbus, OH 43210; Department of Chemistry and Biochemistry, Ohio Northern University, Ada, OH 45810To whom correspondence should be addressed; Departments of Molecular and Cellular Biochemistry Ohio State University, Columbus, OH 43210; Institute for Mitochondrial Biology, Ohio State University, Columbus, OH 43210; Internal Medicine, Ohio State University, Columbus, OH 43210The effect of electron transport chain redox status on activity of the mitochondrial Ca2+-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.http://www.sciencedirect.com/science/article/pii/S0022227520375027membrane potentialredox statuselectron transport chain inhibitors |
| spellingShingle | Adam J. Rauckhorst Kimberly M. Broekemeier Douglas R. Pfeiffer Regulation of the Ca2-independent phospholipase A2 in liver mitochondria by changes in the energetic state Journal of Lipid Research membrane potential redox status electron transport chain inhibitors |
| title | Regulation of the Ca2-independent phospholipase A2 in liver mitochondria by changes in the energetic state |
| title_full | Regulation of the Ca2-independent phospholipase A2 in liver mitochondria by changes in the energetic state |
| title_fullStr | Regulation of the Ca2-independent phospholipase A2 in liver mitochondria by changes in the energetic state |
| title_full_unstemmed | Regulation of the Ca2-independent phospholipase A2 in liver mitochondria by changes in the energetic state |
| title_short | Regulation of the Ca2-independent phospholipase A2 in liver mitochondria by changes in the energetic state |
| title_sort | regulation of the ca2 independent phospholipase a2 in liver mitochondria by changes in the energetic state |
| topic | membrane potential redox status electron transport chain inhibitors |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520375027 |
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