Biochemistry of Cardiolipin: Sensitivity to Dietary Fatty Acids

Berger, Alvin; Jb, German; Me, Gershwin

doi:10.1016/s1043-4526(08)60118-7

Cited by 19 publications

(25 citation statements)

References 313 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with our current findings, the previously reported ALCAT activities associated with the isolated liver microsomes also lacked exclusivity to linoleoyl-CoA as the acyl donor and recognized both MLCL and DLCL as substrates (24). The physiological significance of the cloned ALCAT1 enzyme involved in cardiolipin remodeling in the ER remains elusive, because the organelle only contains ϳ1% cardiolipin (29). Cardiolipin is localized predominantly, if not exclusively, in mitochondria that contain all of the enzymes necessary for cardiolipin biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

“…Cardiolipin is a predominant glycerophospholipid found in the mitochondria of heart (1,29), and cardiolipin remodeling is believed to play an important role in maintaining normal heart function (39). Hence, decreased cardiolipin levels are associated with heart diseases caused by hyperthyroidism and aging, and development of anticardiolipin antibody is associated with the onset of thrombocytopenia and recurrent thrombosis (1).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Novel Cardiolipin-remodeling Pathway Revealed by a Gene Encoding an Endoplasmic Reticulum-associated Acyl-CoA:Lysocardiolipin Acyltransferase (ALCAT1) in Mouse

Cao

Liu

Lockwood

et al. 2004

Journal of Biological Chemistry

203

235

View full text Add to dashboard Cite

Cardiolipin is a major membrane polyglycerophospholipid that is required for the reconstituted activity of a number of key mitochondrial enzymes involved in energy metabolism. Cardiolipin is subjected to remodeling subsequent to its de novo biosynthesis to attain appropriate acyl composition for its biological functions. Yet, the enzyme(s) involved in the remodeling process have not been identified. We report here the identification and characterization of a murine gene that encodes an acyl-CoA:lysocardiolipin acyltransferase 1 (ALCAT1). Expression of the ALCAT1 cDNA in either insect or mammalian cells led to a significant increase in acylCoA:monolysocardiolipin acyltransferase and acyl-CoA: dilysocardiolipin acyltransferase activities that exhibited a dependence upon ALCAT1 enzyme levels. The recombinant ALCAT1 enzyme recognizes both monolysocardiolipin and dilysocardiolipin as substrates with a preference for linoleoyl-CoA and oleoyl-CoA as acyl donors. In contrast, no significant increases in acyltransferase activities by the recombinant ALCAT1 were detected against either glycerol-3-phosphate or a variety of other lysophospholipids as substrates, including lysophosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidylserine. Immunocytohistochemical analysis showed that the ALCAT1 enzyme is localized in the endoplasmic reticulum, which is supported by a significant ALCAT activity in isolated liver and heart microsomes. Northern blot analysis indicates that the mouse ALCAT1 is widely distributed, with the highest expression in heart and liver. In support of a role for ALCAT1 in maintaining heart function, the ALCAT1 gene is conserved among different species of vertebrates, but not in non-atrium organisms. ALCAT1 represents the first identified cardiolipin-remodeling enzyme from any living organism; its identification implies a novel role for the endoplasmic reticulum in cardiolipin metabolism.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Novel Cardiolipin-remodeling Pathway Revealed by a Gene Encoding an Endoplasmic Reticulum-associated Acyl-CoA:Lysocardiolipin Acyltransferase (ALCAT1) in Mouse

Cao

Liu

Lockwood

et al. 2004

Journal of Biological Chemistry

203

235

View full text Add to dashboard Cite

show abstract

“…Mutation of the PGP synthase gene in Chinese hamster ovary cells caused defective biosynthesis of both PG and cardiolipin, which resulted in mitochondrial dysfunction, which includes defects in the respiratory electron transport chain (14,49,50). Cardiolipin is a predominant glycerophospholipid found in the mitochondria of heart (15,51) and is believed to play an important role in maintaining normal heart function (52). Hence, a reduction in cardiolipin level is associated with heart diseases caused by hyperthyroidism and aging, and development of anti-cardiolipin antibody is associated with onset of thrombocytopenia and recurrent thrombosis (15).…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of a Gene Encoding Human LPGAT1, an Endoplasmic Reticulum-associated Lysophosphatidylglycerol Acyltransferase

Yang

Cao

Shi

2004

Journal of Biological Chemistry

100

View full text Add to dashboard Cite

Phosphatidylglycerol (PG) is an important membrane polyglycerolphospholipid required for the activity of a variety of enzymes and is a precursor for synthesis of cardiolipin and bis(monoacylglycerol) phosphate. PG is subjected to remodeling subsequent to its de novo biosynthesis to incorporate appropriate acyl content for its biological functions and to prevent the harmful effect of lysophosphatidylglycerol (LPG) accumulation. The enzymes involved in the remodeling process have not yet been identified. We report here the identification and characterization of a human gene encoding an acyl-CoA: lysophosphatidylglycerol acyltransferase (LPGAT1). Expression of the LPGAT1 cDNA in Sf9 insect and COS-7 cells led to a significant increase in LPG acyltransferase activity. In contrast, no significant acyltransferase activities were detected against glycerol 3-phosphate or a variety of lysophospholipids, including lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylinositol, and lysophosphatidylserine. The recombinant human LPGAT1 enzyme recognized various acyl-CoAs and LPGs as substrates but demonstrated clear preference to long chain saturated fatty acyl-CoAs and oleoyl-CoA as acyl donors, which is consistent with the lipid composition of endogenous PGs identified from different tissues. Kinetic analyses of LPGAT1 expressed in COS-7 cells showed that oleoyl-LPG was preferred over palmitoyl-LPG as an acyl receptor, whereas oleoylCoA was preferred over lauroyl-CoA as an acyl donor. Consistent with its proposed microsomal origin, LP-GAT1 was localized to the endoplasmic reticulum by subcellular fractionation and immunohistochemical analyses. Northern blot analysis indicated that the human LPGAT1 was widely distributed, suggesting a dynamic functional role of the enzyme in different tissues.

show abstract

“…CL only occurs in mitochondria and plays an important role in the micro-environment of mitochondrial enzymes involved in oxidative phosphorylation, including cytochrome c oxidase, cytochrome bc 1 complex, ATPase, ANT and NADH reductase (Paradies et al, 2002;Schlame et al, 2000). The influence of cardiolipin on the micro-environment of mitochondrial complexes requires certain types of fatty acids (Schlame et al, 2005) and, in mammals, alteration of CL acyl composition modulates the activity of these membrane complexes (Yamaoka et al, 1988;Berger et al, 1993;Watkins et al, 1998). Warm acclimation of rainbow trout led to similar changes in the acyl composition of CL of muscle mitochondria as in carp even if the acyl chain composition differs between these species (Wodtke, 1981b).…”

Section: Phospholipid Classes and Subclasses Restructuringmentioning

confidence: 99%

Changes in mitochondrial oxidative capacities during thermal acclimation of rainbow trout Oncorhynchus mykiss: roles of membrane proteins,phospholipids and their fatty acid compositions

Kraffe

Marty

Guderley

2007

Journal of Experimental Biology

134

116

View full text Add to dashboard Cite

International audienceChanges in the properties of mitochondria from oxidative muscle of rainbow trout Oncorhynchus mykiss were examined during warm (5 degrees C to 15 degrees C) acclimation. Trout were studied shortly after the initial thermal change and after 8 weeks acclimation to 15 degrees C. To identify potential mechanisms by which oxidative capacities change, the modifications of phospholipid composition, membrane proteins and functional capacities of red muscle mitochondria were examined. Marked functional changes of isolated muscle mitochondria during warm acclimation of rainbow trout were reflected by a host of modifications in phospholipid composition, but by few shifts in protein components. Shortly after transfer of trout from 5 degrees C to 15 degrees C, the maximal oxidative capacity of mitochondria measured at 15 degrees C increased slightly, but rates at both assay temperatures (5 degrees C and 15 degrees C) decreased markedly after warm acclimation. The increase in capacity in short-term warm exposed trout was most pronounced when rates at 15 degrees C were expressed relative to cytochrome a and c(1) levels. Non-phosphorylating (State 4) rates of oxygen uptake increased with short-term warm exposure before returning to initial levels after warm acclimation. Cytochrome c oxidase (CCO) activity in the mitochondrial preparations decreased with warm acclimation. The thermal sensitivity of the ADP affinity was markedly modified during short-term warm exposure, when the ADP/O ratio increased, but warm acclimation returned these values to those observed initially. ADP affinity increased after warm acclimation. Changes in the mitochondrial content of cytochromes and adenine nucleotide translocase (ANT) could not explain these patterns. On the other hand, changes in the proportions of the lipid classes and in the acyl chain composition of certain phospholipid classes mirror the modifications in functional properties. Short-term exposure to 15 degrees C decreased the ratio of diacylphosphatidylethanolamine/diacylphosphatidylcholine (diacylPE/diacylPC), whereas warm acclimation led to restructuring of fatty acids (FA) and to increases of plasmalogen forms of PE and PC. Modification of overall membrane unsaturation did not appear to be the primary aim of restructuring membrane FA during warm acclimation, as total mitochondrial phospholipids and the major phospholipid classes only showed slight shifts of their acyl composition with warm acclimation. On the other hand, natural lysophosphatidylcholine (LysoPC) showed dramatic changes in FA content, as 16:0 and 18:1n-9 doubled whereas 22:6n-3 decreased from around 50% to 32% in warm acclimated trout. Similarly, in cardiolipin (CL), the levels of 16:0 and 18:1n-7 halved while 18:2n-6 increased to over 20% of the FA with warm acclimation. Given the central role of CL in modulating the activity of CCO, F(0)F(1)-ATPase and ANT, these changes suggest that specific compositional changes in CL are important modulators of mitochondrial capacities. The many structural ...

show abstract

Biochemistry of Cardiolipin: Sensitivity to Dietary Fatty Acids

Cited by 19 publications

References 313 publications

A Novel Cardiolipin-remodeling Pathway Revealed by a Gene Encoding an Endoplasmic Reticulum-associated Acyl-CoA:Lysocardiolipin Acyltransferase (ALCAT1) in Mouse

A Novel Cardiolipin-remodeling Pathway Revealed by a Gene Encoding an Endoplasmic Reticulum-associated Acyl-CoA:Lysocardiolipin Acyltransferase (ALCAT1) in Mouse

Identification and Characterization of a Gene Encoding Human LPGAT1, an Endoplasmic Reticulum-associated Lysophosphatidylglycerol Acyltransferase

Changes in mitochondrial oxidative capacities during thermal acclimation of rainbow trout Oncorhynchus mykiss: roles of membrane proteins,phospholipids and their fatty acid compositions

Contact Info

Product

Resources

About