Acyl-CoA:lysocardiolipin acyltransferase-1

Acyl-CoA:lysocardiolipin acyltransferase-1
Identifiers
Symbol ALCAT1
Alt. symbols LCLAT1, LYCAT
Entrez 253558
HUGO 26756
OMIM 614241
RefSeq NM_182551.3
UniProt Q6UWP7
Other data
Locus Chr. 2 p23.1

Acyl-CoA:lysocardiolipin acyltransferase-1 (ALCAT1) is a polyglycerophospholipid acyltransferase of the endoplasmic reticulum which is primarily known for catalyzing the acylation of monolysocardiolipin back into cardiolipin, although it does catalyze the acylation of other polyglycerophospholipids.[1]

ALCAT1 is widely distributed throughout the body, with the highest concentrations being in the heart and liver.[2]

Function

ALCAT1 facilitates the transfer of acyl groups from linoleoyl-CoA and oleoyl-CoA onto monolysocardiolipin and dilysocardiolipin. The pathway is thought to be important in maintaining heart function, as the ALCAT1 gene is conserved among many species of vertebrates, but not in organisms lacking heart atria.[2]

Recent research has shown that ALCAT1 activity is involved with mitochondrial dysfunction in disease. ALCAT1 is upregulated by oxidative stress and diet-induced obesity, and produces a species of cardiolipin that is highly sensitive to oxidative damage. Deficiency of ALCAT1 prevented the onset of diet-induced obesity, improved mitochondria function, and prevented insulin resistance.[3]

Interactions

ALCAT1 was reported to be regulated by thyroid hormone, a universal regulator of metabolism. Its activity also appeared to be inhibited by the presence of ADP and ATP, but not its analogs or other nucleotides, such as UTP and GTP.[1]

References

  1. 1 2 Cao J, Shen W, Chang Z, Shi Y (April 2009). "ALCAT1 is a polyglycerophospholipid acyltransferase potently regulated by adenine nucleotide and thyroid status". American Journal of Physiology. Endocrinology and Metabolism. 296 (4): E647–53. doi:10.1152/ajpendo.90761.2008. PMC 3734525. PMID 19106248.
  2. 1 2 Cao J, Liu Y, Lockwood J, Burn P, Shi Y (July 2004). "A novel cardiolipin-remodeling pathway revealed by a gene encoding an endoplasmic reticulum-associated acyl-CoA:lysocardiolipin acyltransferase (ALCAT1) in mouse". The Journal of Biological Chemistry. 279 (30): 31727–34. doi:10.1074/jbc.M402930200. PMID 15152008.
  3. ↑ Li J, Romestaing C, Han X, Li Y, Hao X, Wu Y, Sun C, Liu X, Jefferson LS, Xiong J, Lanoue KF, Chang Z, Lynch CJ, Wang H, Shi Y (August 2010). "Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesity". Cell Metabolism. 12 (2): 154–65. doi:10.1016/j.cmet.2010.07.003. PMC 2923392. PMID 20674860.
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