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Publication
Genetic ablation of calcium-independent phospholipase A2gamma leads to
alterations in mitochondrial lipid metabolism and function resulting in a
deficient mitochondrial bioenergetic phenotype.
Authors Mancuso DJ, Sims HF, Han X, Jenkins CM, Guan SP, Yang K, Moon SH, Pietka T,
Abumrad NA, Schlesinger PH, Gross RW
Submitted By Submitted Externally on 7/28/2017
Status Published
Journal The Journal of biological chemistry
Year 2007
Date Published 11/30/2007
Volume : Pages 282 : 34611 - 22
PubMed Reference 17923475
Abstract Previously, we identified a novel calcium-independent phospholipase, designated
calcium-independent phospholipase A(2) gamma (iPLA(2)gamma), which possesses
dual mitochondrial and peroxisomal subcellular localization signals. To identify
the roles of iPLA(2)gamma in cellular bioenergetics, we generated mice null for
the iPLA(2)gamma gene by eliminating the active site of the enzyme through
homologous recombination. Mice null for iPLA(2)gamma display multiple
bioenergetic dysfunctional phenotypes, including 1) growth retardation, 2) cold
intolerance, 3) reduced exercise endurance, 4) greatly increased mortality from
cardiac stress after transverse aortic constriction, 5) abnormal mitochondrial
function with a 65% decrease in ascorbate-induced Complex IV-mediated oxygen
consumption, and 6) a reduction in myocardial cardiolipin content accompanied by
an altered cardiolipin molecular species composition. We conclude that
iPLA(2)gamma is essential for maintaining efficient bioenergetic mitochondrial
function through tailoring mitochondrial membrane lipid metabolism and
composition.




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