The enigmatic role of tafazzin in cardiolipin metabolism

Houtkooper, Riekelt H.; Turkenburg, Marjolein; Poll-Thé, Bwee Tien; Karall, Daniela; Pérez‐Cerdá, Celia; Morrone, Amelia; Malvagia, Sabrina; Wanders, Ronald J. A.; Kulik, Willem; Vaz, Frédéric M.

doi:10.1016/j.bbamem.2009.07.009

Cited by 138 publications

(146 citation statements)

References 66 publications

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“…Additionally, there appeared to be selectivity for 16:1 acyl chains in acyl CoA for hepatic cardiolipin and to even a greater extent for brain cardiolipin; however, no selectivity for 16:1 could be concluded for myocardial cardiolipin. The similarities and differences in acyl selectivity between tissues may result from tissue-specifi c splicing variants or post-translation modifi cations of various known acyltransferases ( 20,38,41,45,52,54 ). Recently, the acyltransferase MLCL AT demonstrated a relative selectivity of 18:2 > 18:1 > 16:1 ( 40 ), which is consistent with the acyl CoA selectivity in the examined heart and liver tissue and also in the examined brain tissue except for 16:1 CoA selectivity.…”

Section: Prediction Of Acyltransferase and Transacylase Activities Assupporting

confidence: 68%

“…these enzymatic activities to the individual pools. It should be emphasized that there exist multiple acyltransferases and transacylases that have demonstrated cardiolipin remodeling activity, and indeed a variety of isoforms have been detected of these enzymes ( 20,38,(51)(52)(53). The current dynamic simulation approach is unable to differentiate these isoform activities yet proposes the relative selectivity of the combined action of various acyltransferases or transacylases.…”

Section: Prediction Of Acyltransferase and Transacylase Activities Asmentioning

confidence: 99%

“…CL, cardiolipin. is commonly believed that acyl CoA as well as PC and PE contribute to the pool of acyl chains used for cardiolipin remodeling in mitochondria ( 20,21,23,24,38,43 ). In addition, Lands cycle remodeling utilizes the sn -2 positions of glycerophospholipids for remodeling ( 49,50 ).…”

Section: Dynamic Simulation Of Hepatic Cardiolipin Molecular Speciesmentioning

confidence: 99%

“…The acyl chains utilized for the formation of mature cardiolipin molecular species could originate from a transacylation reaction from PC or PE or via an acyltransferase reaction from acyl CoA (38)(39)(40). To model these selective aspects of the remodeling machinery, we devised an approach that allows for the input of PC and PE sn -2 positional acyl chain composition as well as acyl CoA chain data utilizing designated acyl chain selectivity ( Fig.…”

Section: Acyl Coa Extraction and Analysismentioning

confidence: 99%

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Dynamic simulation of cardiolipin remodeling: greasing the wheels for an interpretative approach to lipidomics

Kiebish

Bell

Yang

et al. 2010

Journal of Lipid Research

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Lipids are critical for the regulation and control of cellular function, membrane dynamics, and signal transduction. The systematic identifi cation and analysis of all cellular lipids in a biological sample is embodied by the rapidly developing fi eld of lipidomics, which has been enabled by recent advances in mass spectrometry ( 1-3 ). A multidimensional MS-based shotgun lipidomics (MDMS-SL) approach for analysis of cellular lipidomes has been demonstrated as one of the most systematic and quantitative high-throughput platforms for global lipidomics capable of analyzing thousands of lipid molecular species directly from the lipid extracts of biological tissues ( 4, 5 ). Analysis of lipidomic data requires extensive use of bioinformatics and computational algorithms for the accurate identifi cation and quantifi cation of lipid molecular species and classes ( 5-9 ). However, most advances in bioinformatics in lipidomics have largely focused on lipid identifi cation rather than interpretation of alterations in biological function resulting in adaptive or pathologic changes in lipid metabolism ( 10 ). Thus, development of bioinformatic and systems biology approaches for the interpretation of lipidomic networks would signifi cantly advance the understanding of the roles of lipids in biological systems ( 3 ).Cardiolipin is a complex polyglycerophospholipid found almost exclusively in mitochondrial membranes of eukaryotic organisms ( 11 ). Cardiolipin is intricately involved in the effi cient production of ATP through utilizing the proton gradient as well as maintaining mitochondrial functionality ( 12-14 ). The diversity of cardiolipin molecular species varies markedly between tissues as well as among Abstract Cardiolipin is a class of mitochondrial specifi c phospholipid, which is intricately involved in mitochondrial functionality. Differences in cardiolipin species exist in a variety of tissues and diseases. It has been demonstrated that the cardiolipin profi le is a key modulator of the functions of many mitochondrial proteins. However, the chemical mechanism(s) leading to normal and/or pathological distribution of cardiolipin species remain elusive. Herein, we describe a novel approach for investigating the molecular mechanism of cardiolipin remodeling through a dynamic simulation. This approach applied data from shotgun lipidomic analyses of the heart, liver, brain, and lung mitochondrial lipidomes to model cardiolipin remodeling, including relative content, regiospecifi city, and isomeric composition of cardiolipin species. Generated cardiolipin profi les were nearly identical to those determined by shotgun lipidomics. Importantly, the simulated isomeric compositions of cardiolipin species were further substantiated through product ion analysis. Finally, unique enzymatic activities involved in cardiolipin remodeling were assessed from the parameters used in the dynamic simulation of cardiolipin profi les. Collectively, we described, verifi ed, and demonstrated a novel approach by integrating both lipidomic ana...

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Section: Prediction Of Acyltransferase and Transacylase Activities Assupporting

confidence: 68%

Section: Prediction Of Acyltransferase and Transacylase Activities Asmentioning

confidence: 99%

Section: Dynamic Simulation Of Hepatic Cardiolipin Molecular Speciesmentioning

confidence: 99%

Section: Acyl Coa Extraction and Analysismentioning

confidence: 99%

See 2 more Smart Citations

Dynamic simulation of cardiolipin remodeling: greasing the wheels for an interpretative approach to lipidomics

Kiebish

Bell

Yang

et al. 2010

Journal of Lipid Research

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“…2 BTHS is caused by mutations in the TAZ gene at Xq28, 7 which encodes tafazzin, an acyltransferase which promotes molecular symmetry among cardiolipin (CL) species with different fatty acyl moieties. 8,9 CL is involved in the mitochondrial energy metabolism, mitochondrial dynamics and triggering of apoptotic pathways. 10,11 In mammalian cardiac and skeletal muscle, the predominant form is tetralinoleoyl cardiolipin (L4-CL).…”

Section: Introductionmentioning

confidence: 99%

Intra-individual plasticity of the TAZ gene leading to different heritable mutations in siblings with Barth syndrome

et al. 2015

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Infantile-onset skeletal myopathy Barth syndrome (OMIM #302060) is caused by mutations in the X-linked TAZ gene and hence usually manifests itself only in hemizygous males. Confirmatory testing is provided by mutational analysis of the TAZ gene and/or by biochemical dosage of the monolysocardiolipin/tetralinoleoyl cardiolipin ratio. Heterozygous females do not usually display a clinical phenotype but may undergo molecular genetic prenatal diagnosis during pregnancy. We characterized two novel and non-identical TAZ gene rearrangements in the offspring of a single female carrier of Barth syndrome. The hg19chrX:g.153634427_153644361delinsKP_123427.1 TAZ gene rearrangement was identified in her affected son, whereas the NM_000116.3(TAZ)c. − 72_109+51del TAZ gene deletion was identified in a male foetus during a subsequent pregnancy. The unaffected mother was surprisingly found to harbour both variants in addition to a wild-type TAZ allele. A combination of breakpoint junction sequencing, linkage analysis and assessment of allelic dosage revealed that the two variants had originated independently from an apparently unstable/mutable TAZ maternal allele albeit via different mutational mechanisms. We conclude that molecular prenatal diagnosis in Barth syndrome families with probands carrying TAZ gene rearrangements should include investigation of the entire coding region of the TAZ gene. The identification of the breakpoint junctions of such gross gene rearrangements is important to ensure accurate ascertainment of carriership with a view to providing appropriate genetic counselling.

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Bacteria, yeast, worms, and flies: Exploiting simple model organisms to investigate human mitochondrial diseases

Rea

Graham

Nakamaru‐Ogiso

et al. 2010

Dev Disabil Res Revs

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The extensive conservation of mitochondrial structure, composition, and function across evolution offers a unique opportunity to expand our understanding of human mitochondrial biology and disease. By investigating the biology of much simpler model organisms, it is often possible to answer questions that are unreachable at the clinical level. Here, we review the relative utility of four different model organisms, namely the bacteria Escherichia coli, the yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, in studying the role of mitochondrial proteins relevant to human disease. E. coli are single cell, prokaryotic bacteria that have proven to be a useful model system in which to investigate mitochondrial respiratory chain protein structure and function. S. cerevisiae is a single-celled eukaryote that can grow equally well by mitochondrial-dependent respiration or by ethanol fermentation, a property that has proven to be a veritable boon for investigating mitochondrial functionality. C. elegans is a multi-cellular, microscopic worm that is organized into five major tissues and has proven to be a robust model animal for in vitro and in vivo studies of primary respiratory chain dysfunction and its potential therapies in humans. Studied for over a century, D. melanogaster is a classic metazoan model system offering an abundance of genetic tools and reagents that facilitates investigations of mitochondrial biology using both forward and reverse genetics. The respective strengths and limitations of each species relative to mitochondrial studies are explored. In addition, an overview is provided of major discoveries made in mitochondrial biology in each of these four model systems.

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The enigmatic role of tafazzin in cardiolipin metabolism

Cited by 138 publications

References 66 publications

Dynamic simulation of cardiolipin remodeling: greasing the wheels for an interpretative approach to lipidomics

Dynamic simulation of cardiolipin remodeling: greasing the wheels for an interpretative approach to lipidomics

Intra-individual plasticity of the TAZ gene leading to different heritable mutations in siblings with Barth syndrome

Bacteria, yeast, worms, and flies: Exploiting simple model organisms to investigate human mitochondrial diseases

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