Turnover of nonessential fatty acids in cardiolipin from the rat heart

Paulin N Wahjudi,Jennifer K Yee,Steven R Martinez,Jin Zhang,Michael Teitell,Liana Nikolaenko,Ronald Swerdloff,Christina Wang,W.N Paul Lee

doi:10.1194/jlr.m015966

Paulin N Wahjudi, Jennifer K Yee + Show 7 more

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https://doi.org/10.1194/jlr.m015966

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Abstract

Cardiolipin (CL) is a unique phospholipid (PL) found in the mitochondria of mammalian cells. CL remodeling is accompanied by turnover of its fatty acid acyl groups. Abnormalities in CL remodeling have been found in Barth's syndrome, diabetes, and obesity. The objective of this study was to determine nonessential fatty acid turnover in CL and phosphatidylethanolamine (PE) in the rat heart in vivo. Sprague-Dawley rats were fed either a regular chow or a high-fat diet for 15 weeks, and consumed 6% deuterium-enriched drinking water as a tracer for 14 days. CL and PE were extracted from cardiac tissue and isolated by TLC. Fatty acids from CL, PE, and plasma were analyzed by GC/MS for deuterium incorporation. Results showed oleate and vaccenate turnover were the highest in CL whereas palmitate and stearate turnover were low. Among the nonessential fatty acids in PE, turnover of stearate and vaccenate were the highest. The high turnover rate in vaccenate was unexpected, because vaccenate previously had no known metabolic or physiologic function. In conclusion, the similarly high turnover rates of both oleate and vaccenate readily suggest that remodeling is an important functional aspect of PL metabolism in CL.

Highlights

Cardiolipin (CL) is a unique phospholipid (PL) found in the mitochondria of mammalian cells
The ratio of fraction of new synthesis (FNS) in a fatty acid from CL or PE to the FNS of the respective fatty acids in plasma represents relative turnover of these fatty acids in CL and PE by synthesis or remodeling during the 14 day period. These ratios are Cardiolipin is a unique phospholipid found in the mitochondrial membrane
CL interacts with membrane proteins enabling numerous mitochondrial functions such as oxidative phosphorylation, transport of ATP/ ADP, and apoptosis [36]

Summary

Introduction

Cardiolipin (CL) is a unique phospholipid (PL) found in the mitochondria of mammalian cells. CL remodeling is accompanied by turnover of its fatty acid acyl groups. The objective of this study was to determine nonessential fatty acid turnover in CL and phosphatidylethanolamine (PE) in the rat heart in vivo. Among the nonessential fatty acids in PE, turnover of stearate and vaccenate were the highest. The high turnover rates of both oleate and vaccenate readily suggest that remodeling is an important functional aspect of PL metabolism in CL.—P. N. Paul Lee. Turnover of nonessential fatty acids in cardiolipin from the rat heart. It has been proposed that synthesis of CL is via conversion of phosphatidic acid into cytidinediphosphate-diacylglycerol (CDP-DAG) in the mitochondria, which forms phosphatidylglycerolphosphate (PGP). The first proposed pathway incorporates acyl-CoAs in the presence of monolysocardiolipin acyltransferase (MLCL AT) [18,19,20]. Another proposed pathway, referred to as transacylation, has been reported in which acyl groups are directly transferred from phospholipids into MLCL [21,22,23]

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