Tafazzin

Tafazzin
Identifiers
Symbols	TAZ ; BTHS; CMD3A; EFE; EFE2; G4.5; LVNCX; Taz1
External IDs	OMIM: 300394 MGI: 109626 HomoloGene: 37264 GeneCards: TAZ Gene
EC number	2.3.1.23
Gene ontology Molecular function • 1-acylglycerophosphocholine O-acyltransferase activity Cellular component • nucleus • mitochondrion • mitochondrial inner membrane • cytosol • integral component of membrane • intrinsic component of membrane • mitochondrial membrane Biological process • phospholipid metabolic process • muscle contraction • heart development • skeletal muscle tissue development • hemopoiesis • cardiolipin biosynthetic process • mitochondrial respiratory chain complex I assembly • cardiolipin acyl-chain remodeling • cristae formation • mitochondrial ATP synthesis coupled electron transport • small molecule metabolic process • glycerophospholipid biosynthetic process • cardiac muscle tissue development • cardiac muscle contraction Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6901	66826
Ensembl	ENSG00000102125	ENSMUSG00000009995
UniProt	Q16635	I7HJS2
RefSeq (mRNA)	NM_000116	NM_001173547
RefSeq (protein)	NP_000107	NP_001167018
Location (UCSC)	Chr X: 154.41 – 154.42 Mb	Chr X: 74.28 – 74.29 Mb
PubMed search

Tafazzin is a protein that in humans is encoded by the TAZ gene.^[1] Tafazzin is highly expressed in cardiac and skeletal muscle. It is involved in the metabolism of cardiolipin.^[2]

Tafazzin functions as a phospholipid-lysophospholipid transacylase.^[3][4]

Pathology

The mutation of the tafazzin gene is associated with a number of clinical disorders including Barth syndrome (BTHS) (type II 3-Methylglutaconic aciduria), dilated cardiomyopathy (DCM), hypertrophic DCM, endocardial fibroelastosis, and left ventricular noncompaction (LVNC). Tafazzin is responsible for remodeling of a phospholipid cardiolipin (CL),^[5] the signature lipid of the mitochondrial inner membrane. As a result, BTHS patients exhibit defects in CL metabolism, including aberrant CL fatty acyl composition, accumulation of monolysocardiolipin (MLCL) and reduced total CL levels.^[6][7]

History

The protein was identified by Italian scientists Silvia Bione et al. in 1996.^[8] Owing to the complex procedure required for the identification of tafazzin, the protein was named after "Tafazzi", a masochistic comic character in an Italian television show.

References

1. "Entrez Gene: tafazzin".
2. Malhotra A, Xu Y, Ren M, Schlame M (April 2009). "Formation of molecular species of mitochondrial cardiolipin. 1. A novel transacylation mechanism to shuttle fatty acids between sn-1 and sn-2 positions of multiple phospholipid species". Biochim. Biophys. Acta 1791 (4): 314–20. doi:10.1016/j.bbalip.2009.01.004. PMC 2679859. PMID 19416660.
3. Xu Y, Zhang S, Malhotra A, et al. (October 2009). "Characterization of Tafazzin Splice Variants from Humans and Fruit Flies". J. Biol. Chem. 284 (42): 29230–9. doi:10.1074/jbc.M109.016642. PMC 2781466. PMID 19700766.
4. Xu Y, Malhotra A, Ren M, Schlame M (December 2006). "The enzymatic function of tafazzin". J. Biol. Chem. 281 (51): 39217–24. doi:10.1074/jbc.M606100200. PMID 17082194.
5. Neuwald AF (August 1997). "Barth syndrome may be due to an acyltransferase deficiency". Curr. Biol. 7 (8): R465–6. doi:10.1016/S0960-9822(06)00237-5. PMID 9259571.
6. Barth PG, Wanders RJ, Vreken P, Janssen EA, Lam J, Baas F (June 1999). "X-linked cardioskeletal myopathy and neutropenia (Barth syndrome) (MIM 302060)". J. Inherit. Metab. Dis. 22 (4): 555–67. doi:10.1023/A:1005568609936. PMID 10407787.
7. Valianpour F, Mitsakos V, Schlemmer D, Towbin JA, Taylor JM, Ekert PG, Thorburn DR, Munnich A, Wanders RJ, Barth PG, Vaz FM (June 2005). "Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis". J. Lipid Res. 46 (6): 1182–95. doi:10.1194/jlr.M500056-JLR200. PMID 15805542.
8. Bione S, D'Adamo P, Maestrini E, Gedeon AK, Bolhuis PA, Toniolo D (April 1996). "A novel X-linked gene, G4.5. is responsible for Barth syndrome". Nat. Genet. 12 (4): 385–9. doi:10.1038/ng0496-385. PMID 8630491.

Further reading

• Acehan D, Vaz F, Houtkooper RH, et al. (2011 Jan 14;286(2):899–908.). "Cardiac and Skeletal Muscle Defects in a Mouse Model of Human Barth Syndrome". J Biol Chem. 286 (2): 899–908. doi:10.1074/jbc.M110.171439. PMC 3020775. PMID 21068380. Check date values in: |date= (help)
• "Mouse model of Barth syndrome". SciBX. 3(47); (47). Dec 9, 2010. doi:10.1038/scibx.2010.1427.
• Soustek MS, Falk D, Mah C, Toth M, Schlame M, et al. (2011). "Characterization of a Transgenic Short Hairpin RNA-Induced Murine Model of Tafazzin Deficiency". Hum Gene Ther. 22 (7): 865–71. doi:10.1089/hum.2010.199. PMC 3166794. PMID 21091282.
• Takeda A, Sudo A, Yamada M, Yamazawa H, et al. (2011 Sep 20.). "Barth syndrome diagnosed in the subclinical stage of heart failure based on the presence of lipid storage myopathy and isolated noncompaction of the ventricular myocardium". Eur J Pediatr 170 (11): 1481–4. doi:10.1007/s00431-011-1576-5. PMID 21932011. Check date values in: |date= (help)
• Bachou T, Giannakopoulos A, Trapali C, et al. (2009). "A novel mutation in the G4.5 (TAZ) gene in a Greek patient with Barth syndrome". Blood Cells Mol. Dis. 42 (3): 262–4. doi:10.1016/j.bcmd.2008.11.004. PMID 19261493.
• Gonzalez IL (2005). "Barth syndrome: TAZ gene mutations, mRNAs, and evolution". Am. J. Med. Genet. A 134 (4): 409–14. doi:10.1002/ajmg.a.30661. PMID 15793838.
• Stelzl U, Worm U, Lalowski M, et al. (2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070.
• Barth PG, Valianpour F, Bowen VM, et al. (2004). "X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): an update". Am. J. Med. Genet. A 126A (4): 349–54. doi:10.1002/ajmg.a.20660. PMID 15098233.
• Zimmerman RS, Cox S, Lakdawala NK, et al. (2010). "A novel custom resequencing array for dilated cardiomyopathy". Genet. Med. 12 (5): 268–78. doi:10.1097/GIM.0b013e3181d6f7c0. PMC 3018746. PMID 20474083.
• Malhotra A, Edelman-Novemsky I, Xu Y, et al. (2009). "Role of calcium-independent phospholipase A2 in the pathogenesis of Barth syndrome". Proc. Natl. Acad. Sci. U.S.A. 106 (7): 2337–41. doi:10.1073/pnas.0811224106. PMC 2650157. PMID 19164547.
• van Werkhoven MA, Thorburn DR, Gedeon AK, Pitt JJ (2006). "Monolysocardiolipin in cultured fibroblasts is a sensitive and specific marker for Barth Syndrome". J. Lipid Res. 47 (10): 2346–51. doi:10.1194/jlr.D600024-JLR200. PMID 16873891.
• Acehan D, Xu Y, Stokes DL, Schlame M (2007). "Comparison of lymphoblast mitochondria from normal subjects and patients with Barth syndrome using electron microscopic tomography". Lab. Invest. 87 (1): 40–8. doi:10.1038/labinvest.3700480. PMC 2215767. PMID 17043667.
• Barth PG, Wanders RJ, Vreken P, et al. (1999). "X-linked cardioskeletal myopathy and neutropenia (Barth syndrome) (MIM 302060)". J. Inherit. Metab. Dis. 22 (4): 555–67. doi:10.1023/A:1005568609936. PMID 10407787.
• Claypool SM, Boontheung P, McCaffery JM, et al. (2008). "The Cardiolipin Transacylase, Tafazzin, Associates with Two Distinct Respiratory Components Providing Insight into Barth Syndrome". Mol. Biol. Cell 19 (12): 5143–55. doi:10.1091/mbc.E08-09-0896. PMC 2592642. PMID 18799610.
• Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
• McKenzie M, Lazarou M, Thorburn DR, Ryan MT (2006). "Mitochondrial respiratory chain supercomplexes are destabilized in Barth Syndrome patients". J. Mol. Biol. 361 (3): 462–9. doi:10.1016/j.jmb.2006.06.057. PMID 16857210.
• Lu B, Kelher MR, Lee DP, et al. (2004). "Complex expression pattern of the Barth syndrome gene product tafazzin in human cell lines and murine tissues". Biochem. Cell Biol. 82 (5): 569–76. doi:10.1139/o04-055. PMID 15499385.
• Ma L, Vaz FM, Gu Z, et al. (2004). "The human TAZ gene complements mitochondrial dysfunction in the yeast taz1Delta mutant. Implications for Barth syndrome". J. Biol. Chem. 279 (43): 44394–9. doi:10.1074/jbc.M405479200. PMID 15304507.
• Xu Y, Zhang S, Malhotra A, et al. (2009). "Characterization of Tafazzin Splice Variants from Humans and Fruit Flies". J. Biol. Chem. 284 (42): 29230–9. doi:10.1074/jbc.M109.016642. PMC 2781466. PMID 19700766.
• Houtkooper RH, Turkenburg M, Poll-The BT, et al. (2009). "The enigmatic role of tafazzin in cardiolipin metabolism". Biochim. Biophys. Acta 1788 (10): 2003–14. doi:10.1016/j.bbamem.2009.07.009. PMID 19619503.
• Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to Biology: A Functional Genomics Pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• Saunders MA, Slatkin M, Garner C, et al. (2005). "The Extent of Linkage Disequilibrium Caused by Selection on G6PD in Humans". Genetics 171 (3): 1219–29. doi:10.1534/genetics.105.048140. PMC 1456824. PMID 16020776.
• Vaz FM, Houtkooper RH, Valianpour F, et al. (2003). "Only one splice variant of the human TAZ gene encodes a functional protein with a role in cardiolipin metabolism". J. Biol. Chem. 278 (44): 43089–94. doi:10.1074/jbc.M305956200. PMID 12930833.

External links

• GeneReviews/NCBI/NIH/UW entry on Dilated Cardiomyopathy Overview
• TAZ protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)