Turnover of fatty acids in rat liver cardiolipin: Comparison with other mitochondrial phospholipids

Landriscina, C; Megli, Francesco M.; Quagliariello, Ernesto

doi:10.1007/bf02532585

Cited by 45 publications

(24 citation statements)

References 46 publications

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“…This was first observed in rats labeled with 32 P phosphate [66] or 2 H 2 O [67] and later confirmed in cell cultures and flies [45, 68]. For instance, there is no measurable CL turnover in Drosophila over a period of 9 days, which is remarkable given that these animals only live 60 days and show plenty of turnover in all other phospholipids during the 9 day period [45].…”

Section: Turnover Of CLmentioning

confidence: 83%

Biosynthesis, remodeling and turnover of mitochondrial cardiolipin

Schlame

Greenberg

2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

180

152

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Among mitochondrial lipids, cardiolipin occupies a unique place. It is the only phospholipid that is specific to mitochondria and although it is merely a minor component, accounting for 10–20% of the total phospholipid content, cardiolipin plays an important role in the molecular organization, and thus the function of the cristae. This review covers the formation of cardiolipin, a phospholipid dimer containing two phosphatidyl residues, and its assembly into mitochondrial membranes. While a large body of literature exists on this topic, the review focuses on papers that appeared in the past three years.

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Section: Turnover Of CLmentioning

confidence: 83%

Biosynthesis, remodeling and turnover of mitochondrial cardiolipin

Schlame

Greenberg

2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

180

152

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“…The turnover of linoleic acid is higher than that of nonessential fatty acids; and the turnover of either acyl group is higher than the turnover of glycerol phosphate ( 24 ). Even though CL is a structural lipid, a critical component of the mitochondria inner membrane, the dynamics of fatty acid turnover in CL suggests that the remodeling process is very active and may play a functional role in the regulation of mitochondrial metabolism.…”

Section: Spectral Data Analysismentioning

confidence: 98%

“…The turnover of nonessential fatty acids was previously investigated using a bolus injection of 14 C-acetate intraperitoneally ( 24 ). In that study, 14 C-acetate was incorporated into nonessential fatty acids, and the decay of 14 C activity in cardiolipin was used as a measure of the nonessential fatty acids turnover.…”

Section: Spectral Data Analysismentioning

confidence: 99%

Turnover of nonessential fatty acids in cardiolipin from the rat heart

Wahjudi

Yee

Martinez

et al. 2011

Journal of Lipid Research

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This article is available online at http://www.jlr.org glycerols and four acyl groups, forming a dimeric structure with a glycerol linker between two phosphotidyl groups, providing a pair of sn1 and sn2 positions per CL molecule. In mammals, CL fatty acid composition is dominated by linolenic acid on the sn1 positions whereas the sn2 positions are occupied by monounsaturated, di-unsaturated, and polyunsaturated fatty acids ( 1-4 ). A symmetrical tetra-acyl CL has also been identifi ed with linolenic acid at the two sn1 and sn2 positions ( 5, 6 ). CL is a specifi c marker of mitochondria where it appears to play multiple roles related to energy transformation, apoptosis, and membrane integrity ( 7-12 ).It has been proposed that synthesis of CL is via conversion of phosphatidic acid into cytidinediphosphate-diacylglycerol (CDP-DAG) in the mitochondria, which then forms phosphatidylglycerolphosphate (PGP). PGP is converted to phosphatidylglycerol which then reacts with another molecule of CDP-DAG in presence of CL synthase to form CL ( 13-17 ). In order for CL to achieve its specifi c acyl composition, synthesized CL undergoes acyl chain remodeling with monolysocardiolipin (MLCL) as an intermediate. There are two proposed mechanisms for remodeling of CL from MLCL. The fi rst 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 ( 21-23 ).Fatty acids are either incorporated into the nascent CL backbone via CDP-DAG during its biosynthesis or its subsequent remodeling by MLCL AT. Specifi c composition of acyl groups within the sn1 and sn2 positions may be fi nalized through the process of transacylation. The fatty acids 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% deuteriumenriched 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...

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“…The remodeling idea was suggested by (i) lack of acyl specificity in the de novo pathway (25,26), (ii) independent turnover of acyl and glycerol moieties of CL (27), and (iii) presence of lyso-CLs in mitochondria (23). The classical mechanism of phospholipid remodeling is the Lands cycle in which endogenous fatty acids are removed from phospholipids by phospholipase A 2 and new fatty acids are re-attached by acyl-CoA:lysophospholipid acyltransferase.…”

mentioning

confidence: 99%

Remodeling of Cardiolipin by Phospholipid Transacylation

Kelley

Blanck

et al. 2003

Journal of Biological Chemistry

186

196

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Mitochondrial cardiolipin (CL) contains unique fatty acid patterns, but it is not known how the characteristic molecular species of CL are formed. We found a novel reaction that transfers acyl groups from phosphatidylcholine or phosphatidylethanolamine to CL in mitochondria of rat liver and human lymphoblasts. Acyl transfer was stimulated by ADP, ATP, and ATP␥S, but not by other nucleotides. Coenzyme A stimulated the reaction only in the absence of adenine nucleotides. Free fatty acids were not incorporated into CL under the same incubation condition. The transacylation required addition of exogenous CL or monolyso-CL, whereas dilyso-CL was not a substrate. Transacylase activity was decreased in lymphoblasts from patients with Barth syndrome (tafazzin deletion), and this was accompanied by drastic changes in the molecular composition of CL. In rat liver, where linoleic acid was the most abundant residue of CL, only linoleoyl groups were transferred into CL, but not oleoyl or arachidonoyl groups. We demonstrated complete remodeling of tetraoleoyl-CL to tetralinoleoyl-CL in rat liver mitochondria and identified the intermediates linoleoyl-trioleoyl-CL, dilinoleoyl-dioleoyl-CL, and trilinoleoyl-oleoyl-CL by high-performance liquid chromatography. The data suggest that CL is remodeled by acyl specific phospholipid transacylation and that tafazzin is an acyltransferase involved in this mechanism.

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Turnover of fatty acids in rat liver cardiolipin: Comparison with other mitochondrial phospholipids

Cited by 45 publications

References 46 publications

Biosynthesis, remodeling and turnover of mitochondrial cardiolipin

Biosynthesis, remodeling and turnover of mitochondrial cardiolipin

Turnover of nonessential fatty acids in cardiolipin from the rat heart

Remodeling of Cardiolipin by Phospholipid Transacylation

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