Purification and Characterization of Monolysocardiolipin Acyltransferase from Pig Liver Mitochondria

Taylor, William A.; Hatch, Grant M.

doi:10.1074/jbc.m210329200

Cited by 72 publications

(84 citation statements)

References 40 publications

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“…In contrast, acyl-CoA-dependent acyltransferases only distinguish between saturated and unsaturated fatty acids (34,35). This is also true for purified MLCL:acyl-CoA acyltransferase from liver mitochondria (28). Although this enzyme cannot provide specific incorporation of linoleoyl groups into CL, it may still be involved in the remodeling process.…”

Section: Remodeling Of CL In Rat Livermentioning

confidence: 95%

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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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Section: Remodeling Of CL In Rat Livermentioning

confidence: 95%

“…This process requires activation of fatty acids by MgATP and CoA. Acyl-CoA:MLCL acyltransferase activity has been identified in liver and heart, but it failed to show the anticipated linoleoyl specificity (24,28). In this paper we report that acyl groups can be transferred directly from phosphatidylcholine (PC) or phosphatidylethanolamine (PE) to CL.…”

mentioning

confidence: 93%

Remodeling of Cardiolipin by Phospholipid Transacylation

Kelley

Blanck

et al. 2003

Journal of Biological Chemistry

186

196

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“…Mitochondrial CL was shown to be remodeled by a deacylationreacylation cycle in which newly synthesized CL was rapidly deacylated to MLCL and then reacylated back to CL with linoleoyl-CoA (19). A mitochondrial MLCL acyltransferase (MLCL AT) activity was characterized and purified from pig liver mitochondria (20,21). An acyl-CoA-dependent reacylation of MLCL to CL was shown to occur in rat liver microsomes (22).…”

Section: Cardiolipin (Cl)mentioning

confidence: 99%

Identification of the Human Mitochondrial Linoleoyl-coenzyme A Monolysocardiolipin Acyltransferase (MLCL AT-1)

Taylor

Hatch

2009

Journal of Biological Chemistry

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100

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Here we report the identification of a previously uncharacterized human protein as the human monolysocardiolipin acyltransferase-1 (MLCL AT-1). Pig liver mitochondria were treated with n-butyl alcohol followed by Q-Sepharose chromatography, preparative gel electrophoresis, cytidine diphosphate-1,2-diacyl-sn-glycerol-Sepharose chromatography, and finally monolysocardiolipin-adriamycin-agarose affinity chromatography. Elution with either monolysocardiolipin or linoleoyl coenzyme A revealed a major band at 74 kDa with high specific activity (2,300 pmol/min/mg) for the acylation of monolysocardiolipin to cardiolipin using Cardiolipin (CL)2 is a major phospholipid found in mammalian mitochondria with a multitude of biological functions (reviewed in Refs. 1-7). For example, CL is responsible for modulation of the activity of several mitochondrial enzymes involved in the generation of ATP (reviewed in Refs. 8, 9). In fact, it has been suggested that CL is the "glue" that holds the mitochondrial respiratory complex together (10). The role of CL in genetic diseases such as Barth syndrome, a rare X-linked genetic disorder, is beginning to emerge. Barth syndrome is the only known genetic disease in which the specific biochemical defect is a reduction in CL and accumulation of monolysocardiolipin (MLCL) caused by mutations in the TAZ gene (reviewed in Refs. 2,7,11,12). In addition, the role that CL plays in apoptosis is now well documented (reviewed in Ref. 13). Thus, maintenance of the appropriate content and fatty acyl composition of CL in mitochondria is essential for proper cellular function.The molecular composition of CL appears to be important for the biological function of CL. In general, there is a selection of a particular kind of fatty acid as well as restriction of the number of fatty acid species (14). The major tetra-acyl molecular species found in rat liver (ϳ57% of total) and bovine heart (ϳ48% of total) are 18:2 in each of the four fatty acyl positions of the cardiolipin molecule. Remodeling of CL is essential to obtain this enrichment of CL with linoleate because CL synthase has no molecular species substrate specificity for cytidine-5Ј-diphosphate-1,2-diacyl-sn-glycerol (15). In addition, the species pattern of CL precursors is similar enough to imply that the enzymes of the CL synthetic pathway are not molecular species-selective (16). Alterations in the molecular composition of CL are associated with various disease states, including diabetes and Barth syndrome (17,18

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“…The monolysocardiolipin acyltransferase 1, primarily purified from mitochondria of pig liver, is a protein with 74 kDa molecular weight and 5.4 isoelectric point, exhibites in vitro monolysocardiolipin acyltransferase activity (Taylor et al, 2003). MLCLA -1 catalyzed linoleoyl-CoA and MLCL to form CL in a ping-pong reaction mechanism.…”

Section: Tafazzin Genementioning

confidence: 99%

“…Human MLCLAT-1(hMLCLAT-1) homologue was identified as a 59 kD unknown protein and showed acyltransferase activity that could reacylate monolysocadiolipin on [ 14 C] linoleoyl residues by an acyl-CoA dependent manner. The identified MLCLAT-1 showed a high activity (10 fold) for unsaturated acyl-CoAs over saturated palmitoyl-CoA, but no specificity for 18:2 substrates was demonstrated (Taylor et al, 2003;Taylor et al, 2009). 3.2.3 Acyl-CoA: Lysocardiolipin Acyltransferase 1 (ALCAT1) ALCAT1, a 1.l kb gene was cloned in 2004. ALCAT1 contains a highly conserved phosphate acyltransferase domain (Plsc), which is also found in the tafazzin gene, thus was predicted to be an acyl-CoA: lysocardiolipin acyltransferase Cao et al, 2004).…”

Section: Tafazzin Genementioning

confidence: 99%

The Role of Cardiolipin Remodeling in Mitochondrial Function and Human Diseases

Yan

Kang²

2011

JMBR

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Cardiolipin (CL), one of bisphosphatidyl glycerol lipid, is found to contain high level of C18:2 acyl chains and exist exclusively in inner membranes of mitochondria. Cardiolipin remodeling is the process for CL to attain its specific acyl chains. With the purpose of introducing this interesting field to readers, in this review, we elucidate the role of cardiolipin in normal functions of mitochondria by analyzing the physical and chemical characters of cardiolipin; we introduce the current models of cardiolipin remodeling by analyzing the enzymes involved in this process; we reviewed the latest progress in the clinical implications of cardiolipin remodeling.

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Purification and Characterization of Monolysocardiolipin Acyltransferase from Pig Liver Mitochondria

Abstract: In mammalian tissues cardiolipin is rapidly remodeled by monolysocardiolipin acyltransferase subsequent to its de novo biosynthesis (Ma, B. J., Taylor

Cited by 72 publications

References 40 publications

Remodeling of Cardiolipin by Phospholipid Transacylation

Remodeling of Cardiolipin by Phospholipid Transacylation

Identification of the Human Mitochondrial Linoleoyl-coenzyme A Monolysocardiolipin Acyltransferase (MLCL AT-1)

The Role of Cardiolipin Remodeling in Mitochondrial Function and Human Diseases

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