Biology:Monolysocardiolipin acyltransferase
| Trifunctional enzyme subunit alpha, mitochondrial | |
|---|---|
| Identifiers | |
| Symbol | HADHA |
| Alt. symbols | MLCL AT-1 |
| NCBI gene | 3030 |
| HGNC | 4801 |
| OMIM | 600890 |
| RefSeq | NP_000173 |
| UniProt | P40939 |
| Other data | |
| EC number | 4.2.1.17 |
| Locus | Chr. 2 p23.3 |
Monolysocardiolipin acyltransferase (MLCL AT-1) is a mitochondrial acyltransferase that facilitates the remodeling of monolysocardiolipin (MLCL) into cardiolipin.
History
In 1990, biologists Michael Schlame and Bernd Rustow observed the deacylation of cardiolipin into MLCL, which was then converted back into cardiolipin by a protein using linoleoyl coenzyme A, derived from phosphatidylcholine.[1] However, acyltransferase activities involved in the reacylation of MLCL had not been identified or characterized in any mammalian tissue until 1999, by the Hatch lab at the University of Manitoba, in rat heart mitochondria.[2] In 2003, the same lab purified and characterized an MLCL acyltransferase in pig liver mitochondria,[3] and by comparing this protein against a human protein database, they identified a sequenced but uncharacterized human protein as the enzyme responsible in 2009.[4]
Function
MLCL AT-1 catalyzes the transfer of the fatty acid chain attached to a coenzyme A molecule to an available hydroxyl group on MLCL, producing cardiolipin. This lipid remodeling is separate from the cardiolipin synthesis pathway, and is essential to maintain its unique unsaturated fatty acyl composition. MLCL AT-1 typically utilizes linoleoyl coenzyme A, preferred to oleoyl coenzyme A, which is preferred to palmitoyl coenzyme A.[4]
Activity during apoptosis
MLCL AT-1 activity increases in cells cardiac myoblast cells exposed to 2-deoxyglucose-induced apoptosis.[5] MLCL AT-1 activity also increases in a rat model of spontaneously hypertensive heart failure.[6] Since cardiolipin content is significantly diminished in the inner mitochondrial membrane during apoptosis, the increase of lipid remodeling by MLCL AT-1 may be an effort of the cell to maintain normal cardiolipin levels.
Similarity to mitochondrial trifunctional protein
MLCL AT-1 is completely identical to the 59-kDa C-terminal end of mitochondrial trifunctional protein HADHA, suggesting the possibility that the two proteins may be the product of alternative splicing of the same gene.[4] MLCL AT-1 is likely a splice variant of the alpha subunit of MTP.[7]
Hormone interaction
Treatment with thyroxine, a thyroid hormone, can produce an almost two-fold increase in MLCL AT-1 activity.[8]
References
- ↑ "Lysocardiolipin formation and reacylation in isolated rat liver mitochondria". The Biochemical Journal 272 (3): 589–95. December 1990. doi:10.1042/bj2720589. PMID 2268287.
- ↑ "Acylation of monolysocardiolipin in rat heart". Journal of Lipid Research 40 (10): 1837–45. October 1999. doi:10.1016/S0022-2275(20)34900-2. PMID 10508203.
- ↑ "Purification and characterization of monolysocardiolipin acyltransferase from pig liver mitochondria". The Journal of Biological Chemistry 278 (15): 12716–21. April 2003. doi:10.1074/jbc.M210329200. PMID 12569106.
- ↑ 4.0 4.1 4.2 "Identification of the human mitochondrial linoleoyl-coenzyme A monolysocardiolipin acyltransferase (MLCL AT-1)". The Journal of Biological Chemistry 284 (44): 30360–71. October 2009. doi:10.1074/jbc.M109.048322. PMID 19737925.
- ↑ "Mitochondrial monolysocardiolipin acyltransferase is elevated in the surviving population of H9c2 cardiac myoblast cells exposed to 2-deoxyglucose-induced apoptosis". Biochemistry and Cell Biology 86 (1): 11–20. February 2008. doi:10.1139/O07-156. PMID 18364741.
- ↑ "Cardiolipin biosynthesis and remodeling enzymes are altered during development of heart failure". Journal of Lipid Research 50 (8): 1600–8. August 2009. doi:10.1194/jlr.M800561-JLR200. PMID 19001357.
- ↑ "Human trifunctional protein alpha links cardiolipin remodeling to beta-oxidation". PLOS ONE 7 (11): e48628. 2012. doi:10.1371/journal.pone.0048628. PMID 23152787.
- ↑ "Thyroxine regulation of monolysocardiolipin acyltransferase activity in rat heart". The Biochemical Journal 346 Pt 2 (2): 403–6. March 2000. doi:10.1042/0264-6021:3460403. PMID 10677359.
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