Monolysocardiolipin acyltransferase

Monolysocardiolipin acyltransferase
Identifiers
Symbol MLCL AT-1
Other data
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

Danos et al. (2008) observed that MLCL AT-1 activity increased in cells cardiac myoblast cells exposed to 2-deoxyglucose-induced apoptosis.[5] In 2009, Saini-Chohan et al. found that MLCL AT-1 activity also increased 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

Taylor & Hatch (2009) also found that MLCL AT-1 is completely identical to the 59-kDa C-terminal end of mitochondrial trifunctional protein, suggesting the possibility that the two proteins may be the product of alternative splicing of the same gene.[4] In 2012, the same lab concluded that MLCL AT-1 is likely a splice variant of the alpha subunit of MTP.[7]

Hormone Interaction

In 2000, Mutter et al. found that treatment with thyroxine, a thyroid hormone, can produce an almost two-fold increase in MLCL AT-1 activity.[8]

References

  1. ↑ Schlame, M; Rüstow, B (1990). "Lysocardiolipin formation and reacylation in isolated rat liver mitochondria". The Biochemical Journal. 272 (3): 589–95. doi:10.1042/bj2720589. PMC 1149749Freely accessible. PMID 2268287.
  2. ↑ Ma, BJ; Taylor, WA; Dolinsky, VW; Hatch, GM (1999). "Acylation of monolysocardiolipin in rat heart". Journal of lipid research. 40 (10): 1837–45. PMID 10508203.
  3. ↑ Taylor, W. A.; Hatch, GM (2003). "Purification and Characterization of Monolysocardiolipin Acyltransferase from Pig Liver Mitochondria". Journal of Biological Chemistry. 278 (15): 12716–21. doi:10.1074/jbc.M210329200. PMID 12569106.
  4. 1 2 3 Taylor, W. A.; Hatch, G. M. (2009). "Identification of the Human Mitochondrial Linoleoyl-coenzyme a Monolysocardiolipin Acyltransferase (MLCL AT-1)". Journal of Biological Chemistry. 284 (44): 30360–71. doi:10.1074/jbc.M109.048322. PMC 2781591Freely accessible. PMID 19737925.
  5. ↑ Danos, Maria; Taylor, William A.; Hatch, Grant M. (2008). "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. doi:10.1139/O07-156. ISSN 0829-8211. PMID 18364741.
  6. ↑ Saini-Chohan, H. K.; Holmes, M. G.; Chicco, A. J.; Taylor, W. A.; Moore, R. L.; McCune, S. A.; Hickson-Bick, D. L.; Hatch, G. M.; Sparagna, G. C. (2008). "Cardiolipin biosynthesis and remodeling enzymes are altered during development of heart failure". The Journal of Lipid Research. 50 (8): 1600–1608. doi:10.1194/jlr.M800561-JLR200. ISSN 0022-2275.
  7. ↑ Beh, Christopher; Taylor, William A.; Mejia, Edgard M.; Mitchell, Ryan W.; Choy, Patrick C.; Sparagna, Genevieve C.; Hatch, Grant M. (2012). "Human Trifunctional Protein Alpha Links Cardiolipin Remodeling to Beta-Oxidation". PLoS ONE. 7 (11): e48628. doi:10.1371/journal.pone.0048628. ISSN 1932-6203. PMC 3494688Freely accessible. PMID 23152787.
  8. ↑ Mutter, Thomas; Dolinsky, Vernon W.; Ma, Brian J.; Taylor, William A.; Hatch, Grant M. (2000). "Thyroxine regulation of monolysocardiolipin acyltransferase activity in rat heart". Biochemical Journal. 346 (2): 403. doi:10.1042/0264-6021:3460403.
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