Affinage

TAFAZZIN

Tafazzin · UniProt Q16635

Length
262 aa
Mass
30.2 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Tafazzin is a mitochondrial CoA-independent phospholipid–lysophospholipid transacylase that remodels cardiolipin, and its loss causes the X-linked disorder Barth syndrome (PMID:8630491, PMID:17082194). The enzyme transfers acyl chains between phospholipids—preferentially exchanging linoleoyl groups between phosphatidylcholine and cardiolipin, and also drawing on plasmenylcholine as a donor—without using CoA or acyl-CoA (PMID:17082194, PMID:29557170). Rather than encoding intrinsic acyl selectivity, tafazzin generates an equilibrium distribution of acyl species whose final composition is dictated by the physical/phase state of its lipid substrates, acting preferentially at non-bilayer lipid domains (PMID:22941046, PMID:28202545); consistent with this, human tafazzin expressed in flies produces a Drosophila acyl pattern (PMID:19700766). Loss of tafazzin reduces total cardiolipin and causes accumulation of monolyso-cardiolipin, and it is this decreased CL/MLCL ratio—not the deficit in unsaturated CL—that drives the physiological defects, since deleting the CL-specific phospholipase Cld1 rescues taz-null cells (PMID:14651618, PMID:24318983). Tafazzin localizes to mitochondria via two independent targeting peptides and is imported through the TOM/small-Tim pathway to face the intermembrane space (PMID:16135531, PMID:29129703); it assembles into distinct complexes with ATP synthase and the adenine nucleotide carrier AAC2 (PMID:18799610). Functionally, tafazzin remodeling is required to stabilize respiratory chain supercomplexes (respirasomes), and its loss destabilizes complex IV-containing supercomplexes, impairs oxidative phosphorylation, increases ROS, and disrupts cristae architecture in a differentiation-dependent manner (PMID:16135531, PMID:23523468, PMID:19114128). Downstream consequences include defective mitophagy initiation, dysregulated CoA-dependent fatty acid and pyruvate oxidation, and impaired myocyte differentiation (PMID:25919711, PMID:32665401, PMID:29694924). Disease-relevant phenotypes trace to these defects: most Barth syndrome missense mutants fail to function and are degraded by the i-AAA protease (PMID:21300850), and tafazzin loss confers cardiac, skeletal-muscle, and neutrophil vulnerabilities, the last via heightened sensitivity to ER stress-mediated apoptosis (PMID:29694924, PMID:34979560).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1996 High

    Established TAFAZZIN (G4.5) as the genetic cause of a human disease, defining the disease locus before any molecular function was known.

    Evidence Mutation analysis identifying stop-codon mutations in Barth syndrome patients

    PMID:8630491

    Open questions at the time
    • Did not reveal the biochemical function of the encoded protein
    • Functional consequences of individual splice isoforms unresolved
  2. 2004 High

    Linked tafazzin to cardiolipin biology by showing a null mutant accumulates monolyso-CL and loses unsaturated CL species, defining its role in CL acyl remodeling rather than de novo synthesis.

    Evidence Yeast taz1Δ null mutant with MS lipid profiling and growth assays

    PMID:14651618

    Open questions at the time
    • Did not establish the enzymatic mechanism directly
    • Did not determine acyl-chain donor specificity
  3. 2005 High

    Located tafazzin topologically and connected its loss to respiratory supercomplex integrity, the first link between CL remodeling and OXPHOS assembly.

    Evidence Subcellular fractionation, protease protection, TOM/Tim import assays, and BN-PAGE supercomplex analysis in yeast

    PMID:16135531

    Open questions at the time
    • Mechanism by which CL remodeling stabilizes supercomplexes not defined
    • Did not address mammalian topology
  4. 2006 High

    Defined the enzymatic activity directly: tafazzin is a CoA-independent, acyl-specific phospholipid–lysophospholipid transacylase favoring PC–CL transfer.

    Evidence In vitro transacylase assay with purified baculovirus-expressed Drosophila tafazzin and radiolabeled substrate transfer

    PMID:17082194

    Open questions at the time
    • Source of acyl-chain specificity not yet explained
    • Did not test plasmalogen or other phospholipid donors
  5. 2008 High

    Mapped tafazzin into discrete physical complexes with ATP synthase and AAC2 and linked its loss to cristae morphology, positioning it within the mitochondrial membrane architecture machinery.

    Evidence Co-IP/MS interactome, BN-PAGE, and electron microscopy of Δtaz1 yeast mitochondria

    PMID:18799610

    Open questions at the time
    • Stoichiometry and function of each complex not resolved
    • Whether complexes reflect catalytic substrate channeling unknown
  6. 2008 Medium

    Connected tafazzin loss to oxidative stress and identified a specific protective lipid species, refining which CL/MLCL derivatives matter physiologically.

    Evidence Protein carbonylation in taz1Δ vs crd1Δ yeast with oleic-acid rescue

    PMID:18430085

    Open questions at the time
    • Direct demonstration that oleoyl-CL/MLCL is the protective species not shown
    • Relevance to mammalian ROS phenotype untested
  7. 2009 High

    Resolved which human splice isoforms are catalytically competent and showed acyl specificity is host-encoded, not enzyme-intrinsic.

    Evidence Isoform expression in HeLa/293T and Drosophila, transacylase assays, CL profiling, and topology experiments

    PMID:19700766

    Open questions at the time
    • Why exon-5 deletion alters membrane integration mechanistically unclear
    • Physiological roles of inactive isoforms unknown
  8. 2011 High

    Explained how Barth missense mutations cause disease: most are non-functional, and a subset is degraded by the i-AAA protease due to misfolding.

    Evidence Systematic yeast complementation of 21 BTHS mutants with BN-PAGE and i-AAA protease epistasis

    PMID:21300850

    Open questions at the time
    • Structural basis of misfolding not defined
    • Whether the same degradation pathway operates in human cells untested
  9. 2012 High

    Provided the physical explanation for acyl specificity—lipid phase state, not enzyme kinetics, drives tetralinoleoyl-CL formation at non-bilayer domains.

    Evidence In vitro transacylation with 31P-NMR lipid-phase characterization and MS species analysis

    PMID:22941046

    Open questions at the time
    • Identity of the privileged non-bilayer domains in vivo not defined
    • How tafazzin is recruited to these domains unknown
  10. 2013 High

    Demonstrated genetically that the low CL/MLCL ratio, not loss of unsaturated CL, is the proximal cause of physiological defects.

    Evidence cld1Δ taz1Δ double-mutant epistasis with growth, lifespan, respiration, and lipid readouts in yeast

    PMID:24318983

    Open questions at the time
    • Molecular basis of MLCL toxicity not defined
    • Whether Cld1 deletion rescues mammalian phenotypes untested
  11. 2013 Medium

    Quantified the supercomplex defect in patient cells and linked tafazzin loss to a block in mitochondrial apoptosis via impaired caspase-8 binding.

    Evidence BN-PAGE, EM, citrate synthase, and flow cytometry in Barth patient lymphoblasts

    PMID:23523468

    Open questions at the time
    • Mechanism connecting CL remodeling to caspase-8 recruitment unresolved
    • Single lab, patient-derived cells only
  12. 2014 Medium

    Placed tafazzin downstream of the Aim24–MICOS axis, identifying an upstream determinant of tafazzin protein levels.

    Evidence Co-IP and CL profiling in aim24 mutant yeast

    PMID:24714493

    Open questions at the time
    • How Aim24/MICOS stabilizes tafazzin mechanistically unknown
    • No mammalian validation
  13. 2015 Medium

    Identified mitophagy initiation as a selective process requiring CL remodeling, distinguishing it from bulk autophagy.

    Evidence Inducible Taz knockdown in primary MEFs with autophagy/mitophagy flux and OXPHOS assays

    PMID:25919711

    Open questions at the time
    • Molecular role of remodeled CL in mitophagosome biogenesis not defined
    • Single lab, two methods
  14. 2015 Medium

    Revealed a non-bioenergetic role in male meiosis and genome integrity, broadening tafazzin's physiological reach.

    Evidence Taz KO mouse chimeras with testis histology, γH2AX, retrotransposon expression, and KO ES germ-cell differentiation

    PMID:26114544

    Open questions at the time
    • Mechanistic link between CL remodeling and meiotic genome stability unclear
    • Whether the defect is mitochondrial-autonomous unknown
  15. 2017 High

    Established quantitatively that tafazzin drives acyl groups toward thermodynamic equilibrium rather than imposing kinetic selectivity.

    Evidence In vitro kinetic and equilibrium analysis with yeast tafazzin and MS quantification

    PMID:28202545

    Open questions at the time
    • How equilibrium tuning produces tissue-specific CL patterns in vivo unresolved
  16. 2017 Medium

    Mapped two independent mitochondrial targeting peptides outside the catalytic cleft, implying some BTHS mutations may act by disrupting localization rather than catalysis.

    Evidence TAZ peptide–eGFP fusions and confocal co-localization in H9c2 cells with CRISPR TAZ-KO controls

    PMID:29129703

    Open questions at the time
    • Which disease mutations disrupt localization not directly tested
    • Relative contribution of each peptide unclear
  17. 2018 High

    Expanded the substrate repertoire by showing plasmenylcholine is a tafazzin donor for CL remodeling and is depleted in deficient hearts.

    Evidence 31P-NMR lipid quantification in TAZ-KD mouse hearts and in vitro transacylation with purified enzyme and plasmalogen substrates

    PMID:29557170

    Open questions at the time
    • Physiological significance of plasmalogen depletion in Barth syndrome unresolved
  18. 2019 Medium

    Identified tafazzin as a vulnerability in acute myeloid leukemia, linking CL/phospholipid remodeling to stemness via TLR signaling.

    Evidence CRISPR screen and genetic TAZ inhibition in AML cells and xenografts with phospholipid and TLR pathway analysis

    PMID:30930145

    Open questions at the time
    • Direct mechanism connecting phosphatidylserine changes to TLR signaling not fully defined
    • Specificity to AML versus other cancers untested
  19. 2019 Medium

    Tied CL remodeling defects to skeletal-muscle differentiation, modeling the myopathy component of Barth syndrome.

    Evidence CRISPR TAZ-KO C2C12 myoblasts with CL profiling, Seahorse respiration, ROS, and differentiation assays

    PMID:29694924

    Open questions at the time
    • Mechanism linking respiratory defect to differentiation block unclear
    • Single cell-line model
  20. 2020 Medium

    Reframed the bioenergetic defect as dysregulation of CoA-dependent intermediary metabolism, partially rescuable by exogenous CoA.

    Evidence Taz-shRNA knockdown mice with substrate oxidation assays, CoA metabolomics, and CoA supplementation

    PMID:32665401

    Open questions at the time
    • How CL/MLCL imbalance lowers mitochondrial CoA mechanistically unknown
    • Relative contribution of CoA defect vs supercomplex defect unresolved
  21. 2022 Medium

    Provided a candidate therapeutic mechanism: SS-31 restores respiratory function and supercomplex organization independently of correcting the MLCL/CL ratio.

    Evidence In vivo SS-31 in TazKD mice with MALDI lipid profiling, respiration, and BN-PAGE

    PMID:36400945

    Open questions at the time
    • Molecular target of SS-31 in this context not defined
    • Durability and disease-modifying effect untested
  22. 2022 Medium

    Explained neutropenia in Barth syndrome by linking tafazzin loss to ER stress-mediated apoptosis in neutrophil progenitors.

    Evidence TAFAZZIN KO mice and ER-Hoxb8 system with transcriptomics and ER stress apoptosis assays

    PMID:34979560

    Open questions at the time
    • Connection between mitochondrial CL defect and ER stress signaling not defined
    • Whether intervention rescues neutrophil numbers untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How tafazzin is recruited to specific non-bilayer lipid domains in vivo, and how a single equilibrium-driving transacylase produces tissue-specific cardiolipin signatures and the diverse downstream phenotypes (mitophagy, CoA metabolism, ER stress), remains unresolved.
  • No structure of human tafazzin bound to substrate
  • Mechanism linking CL/MLCL ratio to supercomplex stabilization, mitophagy, and apoptosis not unified
  • In vivo determinants of acyl-chain specificity per tissue unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0008289 lipid binding 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005739 mitochondrion 3 GO:0005635 nuclear envelope 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 2 R-HSA-9612973 Autophagy 1
Partners
AAC2AIM24ATP SYNTHASEMICOS
Complex memberships
AAC2 (adenine nucleotide carrier) complexATP synthase complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Mutations in the X-linked gene G4.5 (encoding tafazzin proteins produced by alternative splicing) cause Barth syndrome; stop codon mutations interrupt translation of most tafazzin isoforms, establishing G4.5/TAFAZZIN as the disease locus. Mutation analysis (DNA sequencing identifying stop codon mutations) in Barth syndrome patients Nature genetics High 8630491
2006 Drosophila tafazzin functions as a CoA-independent, acyl-specific phospholipid-lysophospholipid transacylase, catalyzing transfer of acyl groups (preferentially linoleoyl) between cardiolipin and phosphatidylcholine without utilizing CoA or acyl-CoA as substrates; the highest rate is for the phosphatidylcholine–cardiolipin transacylation. In vitro transacylase assay using baculovirus-expressed Drosophila tafazzin and affinity-purified MBP-tafazzin fusion protein; radiolabeled substrate transfer; substrate specificity profiling The Journal of biological chemistry High 17082194
2004 Yeast taz1Δ (null mutation in the TAFAZZIN homolog) shows reduced total cardiolipin, accumulation of monolyso-CL, loss of unsaturated CL species (C18:1 and C16:1), and increased de novo CL synthesis without upregulation of CL structural genes CRD1 or PGS1, demonstrating tafazzin's role in cardiolipin remodeling and acyl composition. Yeast genetic model (taz1Δ null mutant); lipid analysis by mass spectrometry/chromatography; growth assays Molecular microbiology High 14651618
2005 Yeast Taz1 (tafazzin ortholog) is an outer mitochondrial membrane protein exposed to the intermembrane space (IMS); its import into mitochondria depends on the TOM receptor Tom5 and the small Tim IMS proteins, but is independent of the SAM complex. TAZ1 deletion destabilizes respiratory chain supercomplexes III2IV2, causing selective release of complex IV monomer and impairing its assembly into supercomplexes. Subcellular fractionation, protease protection assay, import assays with Tom5/Tim mutants; BN-PAGE supercomplex analysis; radiolabeled subunit import into taz1Δ mitochondria Molecular biology of the cell High 16135531
2008 Yeast tafazzin (Taz1p) physically assembles into several distinct protein complexes; ATP synthase and AAC2 are identified in separate stable Taz1p complexes by co-immunoprecipitation/MS. The largest Taz1p complex requires both assembled ATP synthase and cardiolipin. Loss of Taz1p alters cristae morphology similar to ATP synthase oligomer mutants without affecting ATP synthase complex assembly. Co-immunoprecipitation, mass spectrometry (interactome), BN-PAGE, electron microscopy of Δtaz1 mitochondria Molecular biology of the cell High 18799610
2012 Tafazzin's transacylation specificity is determined by the physical state (lipid phase) of its substrates rather than intrinsic enzyme acyl selectivity; tetralinoleoyl-cardiolipin forms only under conditions favoring the inverted hexagonal phase, and substantial transacylation occurs only in non-bilayer lipid aggregates. In isolated mitochondria, <1% of lipids participate in transacylation, suggesting tafazzin acts at privileged non-bilayer lipid domains. In vitro transacylation assay with isolated tafazzin; 31P-NMR characterization of lipid phase; mass spectrometry of molecular species; isolated mitochondria transacylation measurement Nature chemical biology High 22941046
2009 Among human tafazzin splice isoforms, only full-length (FL) and the exon-5-deleted (Δ5) isoforms have transacylase activity in vitro and are able to restore normal cardiolipin pattern and respiratory activity in tafazzin-deficient flies; both localize to mitochondria in HeLa cells, but Δ5 is more integrated into the hydrophobic membrane core. Human tafazzin expression in flies generates cardiolipin with a Drosophila (not human) acyl pattern, indicating acyl specificity is not encoded by tafazzin itself. Expression of isoforms in HeLa/293T and Drosophila; transacylase activity assays; cardiolipin profiling by MS; subcellular fractionation; proteinase K/alkali treatment for topology The Journal of biological chemistry High 19700766
2017 The acyl specificity of the tafazzin reaction results from the physical properties (thermodynamic/packing) of the lipid environment rather than intrinsic enzyme-level kinetic specificity; forward and reverse transacylation rates toward equilibrium are similar across different acyl groups, and tafazzin creates an equilibrium distribution of acyl groups. In vitro transacylation kinetics with yeast tafazzin; comparison of initial rates to equilibrium states across acyl groups; MS quantification of cardiolipin molecular species The Journal of biological chemistry High 28202545
2011 Eighteen of 21 tested Barth syndrome missense mutations in tafazzin fail to functionally replace endogenous Taz1p in yeast. Four BTHS mutant tafazzins are degraded by the IMS AAA (i-AAA) protease due to misfolding; paradoxically these assemble into normal-appearing complexes that are inherently unstable and aggregate upon disassembly. Loss of i-AAA protease partially rescues mutant function. Yeast BTHS mutant panel; functional complementation assays; BN-PAGE complex analysis; i-AAA protease deletion epistasis; protein stability assays The Journal of cell biology High 21300850
2015 TAZ/tafazzin-mediated cardiolipin remodeling is selectively required for the initiation of mitophagy (mitophagosome biogenesis) but not for other autophagic processes; TAZ deficiency in mouse embryonic fibroblasts causes defective mitophagy, impaired oxidative phosphorylation, and severe oxidative stress. Doxycycline-inducible Taz knockdown in primary MEFs; autophagy flux assays; mitophagy-specific assays; oxidative phosphorylation measurements Autophagy Medium 25919711
2013 Deletion of the CL-specific phospholipase Cld1 rescues growth, lifespan, and respiratory defects of the yeast taz1Δ mutant, demonstrating that the decreased CL/MLCL ratio (not deficiency in unsaturated CL) is the primary cause of physiological defects in tafazzin-deficient cells. Genetic epistasis (cld1Δ taz1Δ double mutant); growth and lifespan assays; respiratory measurements; lipid analysis The Journal of biological chemistry High 24318983
2008 Loss of tafazzin (taz1Δ) in yeast causes increased reactive oxygen species (protein carbonylation) specifically during respiratory growth on ethanol; supplementation with oleic acid rescues ethanol sensitivity and reduces oxidative stress in taz1Δ but not crd1Δ, suggesting oleoyl-CL or oleoyl-MLCL mediates this protection. Yeast taz1Δ and crd1Δ mutants; protein carbonylation assay (ROS marker); growth assays; oleic acid supplementation rescue Molecular microbiology Medium 18430085
2014 Aim24, an inner mitochondrial membrane protein interacting with the MICOS complex, is required to maintain tafazzin levels; loss of Aim24 drastically reduces tafazzin protein and alters cardiolipin composition similarly to tafazzin mutants, placing tafazzin functionally downstream of the Aim24–MICOS axis. Co-immunoprecipitation (Aim24–MICOS interaction); protein level analysis; cardiolipin composition by MS in aim24 mutants eLife Medium 24714493
2017 Two distinct peptide sequences within human tafazzin independently direct the protein to mitochondria; these mitochondrial localization signals are not within predicted enzymatic clefts, implying some BTHS mutations may disrupt localization independently of transacylase activity. Sequential TAZ peptide–eGFP fusion protein expression in H9c2 cells; confocal microscopy co-localization with organellar markers; CRISPR TAZ knockout cell lines Journal of molecular and cellular cardiology Medium 29129703
2018 Tafazzin deficiency causes a substantial decrease in plasmenylcholine (plasmalogen) in the heart, in addition to reduced CL and accumulated MLCL; purified tafazzin catalyzes transacylation between lyso-plasmenylcholine/plasmenylcholine and CL/MLCL, establishing plasmenylcholine as a tafazzin substrate for CL remodeling. 31P-NMR lipid quantification in TAZ-KD mouse hearts; in vitro transacylation assay with purified tafazzin and plasmalogen substrates; Western blot for Far1 Biochemistry High 29557170
2020 Tafazzin deficiency in mouse hearts causes deficiencies in mitochondrial CoA and shifts in the acyl-CoA profile that impair fatty acid and pyruvate oxidation (40–60% lower); exogenous CoA partially rescues these oxidation defects, implicating dysregulation of CoA-dependent intermediary metabolism rather than primary respiratory chain defects as the bioenergetic consequence of tafazzin deficiency. Taz-shRNA knockdown mice; mitochondrial substrate oxidation assays; CoA metabolite profiling by LC-MS; CoA supplementation rescue experiments The Journal of biological chemistry Medium 32665401
2019 Tafazzin (TAZ) is necessary for growth and viability of AML cells (identified by CRISPR screen); TAZ inhibition reduces AML stemness and increases differentiation in vitro and in vivo by decreasing cardiolipin and altering global phospholipid levels (including phosphatidylserine), which modulates toll-like receptor (TLR) signaling. CRISPR screen; genetic TAZ inhibition in AML cells in vitro and xenograft in vivo; phospholipid profiling; TLR signaling pathway analysis Cell stem cell Medium 30930145
2015 Mouse tafazzin (Taz) is required for male germ cell meiosis; Taz knockout chimera testes show disruption of spermatocyte progression past the pachytene stage, elevated DNA double-strand damage, and increased endogenous retrotransposon activity, revealing a role for tafazzin in maintaining genome integrity during meiosis. Taz knockout mouse chimeras; histological analysis of testes; DNA damage markers (γH2AX); retrotransposon expression; in vitro germ cell differentiation from KO ES cells PloS one Medium 26114544
2013 Tafazzin knockdown in lymphoblasts from Barth syndrome patients destabilizes the respiratory supercomplex I+III2+IVn (respirasome) and reduces individual complexes I and IV, complex V, and supercomplexes I+III and III+IV; complex III amount and complex II are unaffected. Mitochondrial mass increases as a compensatory response, and the type II (mitochondrial) apoptosis pathway is blocked because mitochondria cannot bind active caspase-8. Immortalized patient lymphoblasts; BN-PAGE supercomplex analysis; electron microscopy; citrate synthase activity; flow cytometry for apoptosis/caspase-8 binding Biochimica et biophysica acta Medium 23523468
2008 Distinct effects of tafazzin deletion on mitochondrial ultrastructure depend on cellular differentiation state: tafazzin deficiency affects cardiolipin in all mitochondria, but significant structural alterations (inner membrane remodeling and aggregation) occur only after specific differentiation, as shown in cardiomyocytes vs. embryonic stem cells and in different Drosophila tissues. Electron tomography of tafazzin-deleted mouse cardiomyocytes, embryonic stem cells, and Drosophila tissues; cardiolipin profiling Mitochondrion Medium 19114128
2022 In vivo treatment with the mitochondria-targeted peptide SS-31 improves mitochondrial respiratory capacity and promotes supercomplex organization in tafazzin-knockdown mouse cardiac mitochondria without affecting the MLCL/CL ratio, suggesting SS-31 acts on respiratory chain function independently of direct CL modification. In vivo SS-31 administration in TazKD mice; MALDI-TOF/MS lipid profiling; mitochondrial respiration assays; BN-PAGE supercomplex analysis Scientific reports Medium 36400945
2019 Tafazzin deletion in C2C12 myoblasts (TAZ-KO) causes accumulation of monolyso-CL, decreased mitochondrial respiration, increased mitochondrial ROS, and impaired myocyte differentiation, linking defective CL remodeling to skeletal myoblast differentiation defects. CRISPR-generated stable tafazzin KO C2C12 cell line; cardiolipin profiling; mitochondrial respiration (Seahorse); ROS measurement; differentiation assays Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 29694924
2022 TAFAZZIN-deficient neutrophil progenitors (in KO mice and ER-Hoxb8 system) show increased sensitivity to ER stress-mediated apoptosis, with transcriptomic upregulation of ER stress markers, providing a mechanistic link between tafazzin loss and neutrophil vulnerability. TAFAZZIN KO mice; ER-Hoxb8 conditional immortalization system; transcriptomic analysis; apoptosis assays with ER stress inducers Blood advances Medium 34979560

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 A novel X-linked gene, G4.5. is responsible for Barth syndrome. Nature genetics 594 8630491
2006 The enzymatic function of tafazzin. The Journal of biological chemistry 278 17082194
1998 Fission yeast Taz1 protein is required for meiotic telomere clustering and recombination. Nature 235 9572143
2001 spRap1 and spRif1, recruited to telomeres by Taz1, are essential for telomere function in fission yeast. Current biology : CB 234 11676925
2006 Semi-conservative DNA replication through telomeres requires Taz1. Nature 217 16598261
2005 Telomere binding protein Taz1 establishes Swi6 heterochromatin independently of RNAi at telomeres. Current biology : CB 184 16243027
2004 Aberrant cardiolipin metabolism in the yeast taz1 mutant: a model for Barth syndrome. Molecular microbiology 176 14651618
2005 Taz1, an outer mitochondrial membrane protein, affects stability and assembly of inner membrane protein complexes: implications for Barth Syndrome. Molecular biology of the cell 174 16135531
1997 The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies. American journal of human genetics 172 9382096
2013 Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation. Biochimica et biophysica acta 146 23523468
2001 The fission yeast Taz1 protein protects chromosomes from Ku-dependent end-to-end fusions. Molecular cell 141 11172711
2009 The enigmatic role of tafazzin in cardiolipin metabolism. Biochimica et biophysica acta 131 19619503
2012 The physical state of lipid substrates provides transacylation specificity for tafazzin. Nature chemical biology 113 22941046
2015 Cardiolipin remodeling by TAZ/tafazzin is selectively required for the initiation of mitophagy. Autophagy 101 25919711
2005 Taz1, Rap1 and Rif1 act both interdependently and independently to maintain telomeres. The EMBO journal 101 16096639
2002 Mutation analysis of the G4.5 gene in patients with isolated left ventricular noncompaction. Molecular genetics and metabolism 100 12468278
2011 Characterization of a transgenic short hairpin RNA-induced murine model of Tafazzin deficiency. Human gene therapy 97 21091282
2003 Interaction of the TAZ1 domain of the CREB-binding protein with the activation domain of CITED2: regulation by competition between intrinsically unstructured ligands for non-identical binding sites. The Journal of biological chemistry 97 14594809
2008 The cardiolipin transacylase, tafazzin, associates with two distinct respiratory components providing insight into Barth syndrome. Molecular biology of the cell 88 18799610
2002 Silencing of the tapetum-specific zinc finger gene TAZ1 causes premature degeneration of tapetum and pollen abortion in petunia. The Plant cell 88 12368491
2004 Neutrophils in Barth syndrome (BTHS) avidly bind annexin-V in the absence of apoptosis. Blood 84 14764526
2008 Loss of tafazzin in yeast leads to increased oxidative stress during respiratory growth. Molecular microbiology 78 18430085
2005 CBP/p300 TAZ1 domain forms a structured scaffold for ligand binding. Biochemistry 71 15641773
1993 Ligand binding to the receptor domain regulates the ratio of kinase to phosphatase activities of the signaling domain of the hybrid Escherichia coli transmembrane receptor, Taz1. Journal of molecular biology 71 8393937
2014 Aim24 and MICOS modulate respiratory function, tafazzin-related cardiolipin modification and mitochondrial architecture. eLife 69 24714493
2005 Ypr140wp, 'the yeast tafazzin', displays a mitochondrial lysophosphatidylcholine (lyso-PC) acyltransferase activity related to triacylglycerol and mitochondrial lipid synthesis. The Biochemical journal 69 15588229
2006 A zebrafish model of human Barth syndrome reveals the essential role of tafazzin in cardiac development and function. Circulation research 68 16794186
2003 The telomere protein Taz1 is required to prevent and repair genomic DNA breaks. Molecular cell 68 12620220
1993 Requirement of both kinase and phosphatase activities of an Escherichia coli receptor (Taz1) for ligand-dependent signal transduction. Journal of molecular biology 68 8389884
2006 Evolutionary-conserved telomere-linked helicase genes of fission yeast are repressed by silencing factors, RNAi components and the telomere-binding protein Taz1. Nucleic acids research 66 16407326
1999 Genetic analysis of the G4.5 gene in families with suspected Barth syndrome. The Journal of pediatrics 65 10484795
2012 Telomere-binding protein Taz1 controls global replication timing through its localization near late replication origins in fission yeast. Genes & development 62 22987637
2008 Distinct effects of tafazzin deletion in differentiated and undifferentiated mitochondria. Mitochondrion 61 19114128
2004 Isolated left ventricular noncompaction is rarely caused by mutations in G4.5, alpha-dystrobrevin and FK Binding Protein-12. Molecular genetics and metabolism 59 15172004
2002 Infantile dilated X-linked cardiomyopathy, G4.5 mutations, altered lipids, and ultrastructural malformations of mitochondria in heart, liver, and skeletal muscle. Laboratory investigation; a journal of technical methods and pathology 58 11896212
2011 Barth syndrome mutations that cause tafazzin complex lability. The Journal of cell biology 57 21300850
2016 Taz1-Shelterin Promotes Facultative Heterochromatin Assembly at Chromosome-Internal Sites Containing Late Replication Origins. Molecular cell 56 27264871
2013 Diminished Exercise Capacity and Mitochondrial bc1 Complex Deficiency in Tafazzin-Knockdown Mice. Frontiers in physiology 56 23616771
2013 Deletion of the cardiolipin-specific phospholipase Cld1 rescues growth and life span defects in the tafazzin mutant: implications for Barth syndrome. The Journal of biological chemistry 55 24318983
2009 Characterization of tafazzin splice variants from humans and fruit flies. The Journal of biological chemistry 53 19700766
2020 The Function of Tafazzin, a Mitochondrial Phospholipid-Lysophospholipid Acyltransferase. Journal of molecular biology 45 32234310
2007 Fission yeast Taz1 and RPA are synergistically required to prevent rapid telomere loss. Molecular biology of the cell 45 17429064
2019 The Mitochondrial Transacylase, Tafazzin, Regulates for AML Stemness by Modulating Intracellular Levels of Phospholipids. Cell stem cell 43 30930145
2014 Mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes. Oxidative medicine and cellular longevity 43 25247053
2019 Role of Backbone Dynamics in Modulating the Interactions of Disordered Ligands with the TAZ1 Domain of the CREB-Binding Protein. Biochemistry 42 30775911
2017 The Basis for Acyl Specificity in the Tafazzin Reaction. The Journal of biological chemistry 40 28202545
2004 Taz1 binding to a fission yeast model telomere: formation of telomeric loops and higher order structures. The Journal of biological chemistry 40 15383525
2019 LINC01413/hnRNP-K/ZEB1 Axis Accelerates Cell Proliferation and EMT in Colorectal Cancer via Inducing YAP1/TAZ1 Translocation. Molecular therapy. Nucleic acids 38 31927328
2012 Taz1 enforces cell-cycle regulation of telomere synthesis. Molecular cell 38 22633956
2004 The CBP/p300 TAZ1 domain in its native state is not a binding partner of MDM2. The Biochemical journal 37 15154850
2018 Loss of tafazzin results in decreased myoblast differentiation in C2C12 cells: A myoblast model of Barth syndrome and cardiolipin deficiency. Biochimica et biophysica acta. Molecular and cell biology of lipids 35 29694924
2020 Tafazzin deficiency impairs CoA-dependent oxidative metabolism in cardiac mitochondria. The Journal of biological chemistry 33 32665401
2018 Substantial Decrease in Plasmalogen in the Heart Associated with Tafazzin Deficiency. Biochemistry 33 29557170
2010 Tafazzin knockdown causes hypertrophy of neonatal ventricular myocytes. American journal of physiology. Heart and circulatory physiology 32 20348225
2007 Recombination-based telomere maintenance is dependent on Tel1-MRN and Rap1 and inhibited by telomerase, Taz1, and Ku in fission yeast. Molecular and cellular biology 31 18160711
2017 Cardiolipin content, linoleic acid composition, and tafazzin expression in response to skeletal muscle overload and unload stimuli. Scientific reports 29 28515468
2014 Optimization and in vivo toxicity evaluation of G4.5 PAMAM dendrimer-risperidone complexes. PloS one 29 24587349
2013 Tafazzin knockdown interrupts cell cycle progression in cultured neonatal ventricular fibroblasts. American journal of physiology. Heart and circulatory physiology 29 23997105
2019 SERCA2a tyrosine nitration coincides with impairments in maximal SERCA activity in left ventricles from tafazzin-deficient mice. Physiological reports 28 31444868
2020 Tafazzin Mutation Affecting Cardiolipin Leads to Increased Mitochondrial Superoxide Anions and Mitophagy Inhibition in Barth Syndrome. Cells 27 33096711
2019 TAZ encodes tafazzin, a transacylase essential for cardiolipin formation and central to the etiology of Barth syndrome. Gene 27 31647997
2018 Aberrant cardiolipin metabolism is associated with cognitive deficiency and hippocampal alteration in tafazzin knockdown mice. Biochimica et biophysica acta. Molecular basis of disease 27 30055293
2018 The transition state structure for binding between TAZ1 of CBP and the disordered Hif-1α CAD. Scientific reports 26 29777197
2020 Biotin-Decorated PAMAM G4.5 Dendrimer Nanoparticles to Enhance the Delivery, Anti-Proliferative, and Apoptotic Effects of Chemotherapeutic Drug in Cancer Cells. Pharmaceutics 25 32403321
2017 Tafazzin (TAZ) promotes the tumorigenicity of cervical cancer cells and inhibits apoptosis. PloS one 25 28489874
2022 Beneficial effects of SS-31 peptide on cardiac mitochondrial dysfunction in tafazzin knockdown mice. Scientific reports 24 36400945
2015 PAMAM G4.5-chlorin e6 dendrimeric nanoparticles for enhanced photodynamic effects. Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology 23 26496965
1994 Transmembrane signaling. Mutational analysis of the cytoplasmic linker region of Taz1-1, a Tar-EnvZ chimeric receptor in Escherichia coli. Journal of molecular biology 23 7990135
2017 Native Hydrophobic Binding Interactions at the Transition State for Association between the TAZ1 Domain of CBP and the Disordered TAD-STAT2 Are Not a Requirement. Biochemistry 22 28707474
2013 Tafazzin splice variants and mutations in Barth syndrome. Molecular genetics and metabolism 22 24342716
2001 A novel intronic mutation of the TAZ ( G4.5) gene in a patient with Barth syndrome: creation of a 5' splice donor site with variant GC consensus and elongation of the upstream exon. Human genetics 22 11735032
2020 Role of Tafazzin in Mitochondrial Function, Development and Disease. Journal of developmental biology 21 32456129
2019 A critical appraisal of the tafazzin knockdown mouse model of Barth syndrome: what have we learned about pathogenesis and potential treatments? American journal of physiology. Heart and circulatory physiology 21 31603701
2017 Establishment of expression-state boundaries by Rif1 and Taz1 in fission yeast. Proceedings of the National Academy of Sciences of the United States of America 21 28096402
2004 Complex expression pattern of the Barth syndrome gene product tafazzin in human cell lines and murine tissues. Biochemistry and cell biology = Biochimie et biologie cellulaire 21 15499385
2020 Investigations of the underlying mechanisms of HIF-1α and CITED2 binding to TAZ1. Proceedings of the National Academy of Sciences of the United States of America 20 32123067
2020 PAMAM G4.5 dendrimers for targeted delivery of ferulic acid and paclitaxel to overcome P-glycoprotein-mediated multidrug resistance. Biotechnology and bioengineering 20 33289076
2023 Genetic modifiers modulate phenotypic expression of tafazzin deficiency in a mouse model of Barth syndrome. Human molecular genetics 19 36917259
2019 Suppression of Tafazzin promotes thyroid cancer apoptosis via activating the JNK signaling pathway and enhancing INF2-mediated mitochondrial fission. Journal of cellular physiology 18 30741413
2019 Downregulation of miR-125b promotes resistance of glioma cells to TRAIL through overexpression of Tafazzin which is a mitochondrial protein. Aging 18 31056533
2015 Structural and functional analyses of Barth syndrome-causing mutations and alternative splicing in the tafazzin acyltransferase domain. Meta gene 18 25941633
2018 Drosophila tafazzin mutants have impaired exercise capacity. Physiological reports 17 29405656
2015 Mouse Tafazzin Is Required for Male Germ Cell Meiosis and Spermatogenesis. PloS one 17 26114544
2015 Acquired deficiency of tafazzin in the adult heart: Impact on mitochondrial function and response to cardiac injury. Biochimica et biophysica acta 16 26692032
2022 A new murine model of Barth syndrome neutropenia links TAFAZZIN deficiency to increased ER stress-induced apoptosis. Blood advances 15 34979560
2020 Competitive binding of HIF-1α and CITED2 to the TAZ1 domain of CBP from molecular simulations. Physical chemistry chemical physics : PCCP 15 32242581
2019 Increased Dynamin-Related Protein 1-Dependent Mitochondrial Fission Contributes to High-Fat-Diet-Induced Cardiac Dysfunction and Insulin Resistance by Elevating Tafazzin in Mouse Hearts. Molecular nutrition & food research 15 30632304
2018 Cardiac mitochondrial structure and function in tafazzin-knockdown mice. Mitochondrion 15 30389594
2021 Tafazzin Deficiency Reduces Basal Insulin Secretion and Mitochondrial Function in Pancreatic Islets From Male Mice. Endocrinology 14 34019639
2018 Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cells. Microbial cell (Graz, Austria) 14 29796387
2010 Gonadal mosaicism of a TAZ (G4.5) mutation in a Japanese family with Barth syndrome and left ventricular noncompaction. Molecular genetics and metabolism 14 20303308
2017 Identification of novel mitochondrial localization signals in human Tafazzin, the cause of the inherited cardiomyopathic disorder Barth syndrome. Journal of molecular and cellular cardiology 13 29129703
2021 The lipid environment modulates cardiolipin and phospholipid constitution in wild type and tafazzin-deficient cells. Journal of inherited metabolic disease 12 34494285
2019 Tafazzin-dependent cardiolipin composition in C6 glioma cells correlates with changes in mitochondrial and cellular functions, and cellular proliferation. Biochimica et biophysica acta. Molecular and cell biology of lipids 12 30639735
2019 Characterization of the dynamics and the conformational entropy in the binding between TAZ1 and CTAD-HIF-1α. Scientific reports 12 31719609
2007 Evaluation of tafazzin as candidate for dilated cardiomyopathy in Irish wolfhounds. The Journal of heredity 12 17621587
2002 Novel missense mutation (R94S) in the TAZ ( G4.5) gene in a Japanese patient with Barth syndrome. Journal of human genetics 12 12032589
2019 Restoration of miR-26b expression partially reverses the cisplatin resistance of NSCLC by targeting tafazzin. OncoTargets and therapy 10 31686855
2018 Effects of siRNA-dependent knock-down of cardiolipin synthase and tafazzin on mitochondria and proliferation of glioma cells. Biochimica et biophysica acta. Molecular and cell biology of lipids 10 29325722
2021 Tafazzin deficiency impairs mitochondrial metabolism and function of lipopolysaccharide activated B lymphocytes in mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 34767647

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