Faculté des sciences

SLC1 and SLC4 encode partially redundant acyl-Coenzyme A 1-acylglycerol-3-phosphate O-acyltransferases of budding yeast

Benghezal, Mohammed ; Roubaty, Carole ; Veepuri, Vijayanath ; Knudsen, Jens ; Conzelmann, Andreas

In: Journal of Biological Chemistry, 2007, p. jbc.M702719200

Phosphatidic acid (PA) is the intermediate, from which all glycerophospholipids are synthesized. In yeast it is generated from lyso-phosphatidic acid, which is acylated by Slc1p, a sn-2-specific, acyl-Coenzyme A-dependent 1-acylglycerol-3-phosphate O-acyltransferase. Deletion of SLC1 is not lethal and does not eliminate all microsomal 1-acylglycerol-3-phosphate O-acyltransferase activity... Plus

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    Summary
    Phosphatidic acid (PA) is the intermediate, from which all glycerophospholipids are synthesized. In yeast it is generated from lyso-phosphatidic acid, which is acylated by Slc1p, a sn-2-specific, acyl-Coenzyme A-dependent 1-acylglycerol-3-phosphate O-acyltransferase. Deletion of SLC1 is not lethal and does not eliminate all microsomal 1-acylglycerol-3-phosphate O-acyltransferase activity suggesting that an additional enzyme may exist. Here we show that SLC4 (Yor175c), a gene of hitherto unknown function, encodes a second 1-acyl-sn-glycerol-3-phosphate acyltransferase. SLC4 harbors a membrane bound O-acyl transferase (MBOAT) motif, and down regulation of SLC4 strongly reduces 1-acyl-sn-glycerol-3-phosphate acyltransferase activity in microsomes from slc1Δ cells. The simultaneous deletion of SLC1 and SLC4 is lethal. Mass spectrometric analysis of lipids from slc1Δ and slc4Δ cells demonstrates that in vivo Slc1p and Slc4p generate almost the same glycerophospholipid profile. Microsomes from slc1Δ and slc4Δ cells incubated with [¹⁴C]-oleoyl-Coenzyme A in the absence of lyso-phosphatidic acid and without CTP still incorporate the label into glycerophospholipids, indicating that Slc1p and Slc4p can also use endogenous lyso-glycerophospholipids as substrates. However, the lipid profiles generated by microsomes from slc1Δ and slc4Δ cells are different and this suggests that Slc1p and Slc4p have a different substrate specificity or have access to different lyso-glycerophospholipid substrates because of a different subcellular location. Indeed, affinity-purified Slc1p displays Mg²⁺-dependent acyltransferase activity not only towards lyso-phosphatidic acid but also lyso forms of phosphatidylserine and phosphatidylinositol. Thus, Slc1p and Slc4p may not only be active as 1-acylglycerol-3-phosphate O-acyltransferases, but also be involved in fatty acid exchange at the sn-2 position of mature glycerophospholipids.