An involvement of phospholipase A/acyltransferase family proteins in peroxisome regulation and plasmalogen metabolism

Abstract

Edited by Wilhelm JustThe H-Ras-like suppressor (HRASLS) is a protein family consisting of five members in humans. Despite their discovery as tumor suppressors, we demonstrated that all these proteins are phospholipid-metabolizing enzymes, such as phospholipase (PL) A 1 /A 2 and acyltransferase. We thus proposed to rename HRASLS1-5 as PLA/acyltransferase (PLAAT)-1-5. Notably, PLAATs exhibit N-acyltransferase activity to biosynthesize N-acylated ethanolamine phospholipids, including N-acyl-plasmalogen, which serve as precursors of bioactive N-acylethanolamines. Furthermore, the overexpression of PLAAT-3 in animal cells causes disappearance of peroxisomes and a remarkable reduction in plasmalogen levels. This finding might be related to the inhibitory effect of PLAAT-3 on the chaperone activity of the peroxin PEX19. In this article, we will review our recent findings about PLAAT proteins, with special reference to their roles in peroxisome biogenesis and plasmalogen metabolism.

Defunctionalizing intracellular organelles such as mitochondria and peroxisomes with engineered phospholipase A/acyltransferases

“…Despite the strong potential, PLAAT3 has features that impeded its readily implementation for synthetic operations in living cells. Consistent with previous reports 17 – 19 , 27 , 28 , full-length PLAAT3 localized to peroxisomes (Supplementary Fig. 3 ), impaired their biogenesis (Supplementary Fig.…”

“…To develop a molecular tool for organelle defunctionalization that is rapidly inducible, generalizable and target-specific, we saw a strong potential in the PLAAT family members 19 . We therefore decide to implement PLAAT proteins in chemically and optically inducible protein dimerization paradigms to reorganize phospholipids of individual organellar membranes.…”

PLAAT1 Exhibits Phosphatidylcholine:Monolysocardiolipin Transacylase Activity

“…These enzymes are also known as lecithin:retinol acyltransferase (LRAT)-like proteins, due to their similar sequence homology to this enzyme [ 8 ], including a conserved NCEHFV motif in the C-terminal region that is critical for acylation and de-acylation reactions [ 31 ]. While all PLAAT family members have previously been reported to have phospholipase A1/2 activity with PC as a substrate, as well as N- and O-transacylase activity using PC as an acyl donor and either PE or lyso-PC, respectively, as acyl acceptors [ 25 , 32 , 33 , 34 , 35 ], activity with MLCL has not previously been reported for this enzyme family.…”

Targeted lipidomics reveals changes in N-acyl serines by acute exposure to an electric field: Molecular insights into the docking of N-18:1 serine interaction with TRPV1 or PPAR-α

“…Little is known about the biosynthesis of N-acyl SERs, though some possible N-acyl EAs biosynthetic pathways have been proposed [33]. Interestingly, a family of phospholipase A/acyltransferase (PLAAT) that contributes to N-acyl EAs formation has been discovered [34]. However, the detailed mechanisms of EF-induced changes in N-18:1 SER, N-16:0 SER, N-18:1 EA, N-16:0 EA, and N-18:2 EA remain to be elucidated.…”