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Regulation of the Ca (2+) -independent phospholipase A (2) in liver mitochondria by changes in the energetic state
Journal article   Open access   Peer reviewed

Regulation of the Ca (2+) -independent phospholipase A (2) in liver mitochondria by changes in the energetic state

Adam J. Rauckhorst, Kimberly M. Broekemeier and Douglas R. Pfeiffer
Journal of lipid research, Vol.55(5), pp.826-836
05/01/2014
DOI: 10.1194/jlr.M043307
PMCID: PMC3995461
PMID: 24586040
url
https://doi.org/10.1194/jlr.M043307View
Published (Version of record) Open Access

Abstract

The effect of electron transport chain redox status on activity of the mitochondrial Ca2+-independent phospholipase A(2) (iPLA(2)) 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 iPLA(2) 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, iPLA(2) activation can be reversed by adding succinate to reestablish a membrane potential. For this purpose, ascorbate plus N,N,NN-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 iPLA(2) accompanies partial deenergization. These findings suggest that in addition to the several functions that have been proposed, the mitochondrial iPLA(2) may help to coordinate local capillary blood flow with changing energy demands.
Biochemistry & Molecular Biology Life Sciences & Biomedicine Science & Technology

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