Phospholipase A and acyltransferases as novel regulator of organelle dynamics

Phospholipase A (PLA) and acyltransferases coordinate glycerophospholipid remodeling to maintain membrane diversity and function. The phospholipase A and acyltransferase (PLAAT) family combines PLA1/PLA2 with N- and O-acyltransferase activities, generating N-acylethanolamines with diverse bioactivities and enabling acyl-CoA-independent remodeling. PLAAT3 has been identified as a causative gene for human lipodystrophy. In addition to adipocyte dysfunction, PLAAT3-deficient mice develop cataracts due to impaired organelle degradation in lens fiber cells. In non-mammalian vertebrates such as zebrafish, which lack PLAAT3, PLAAT1 is highly expressed in the lens, and its deficiency similarly causes cataract-like abnormalities by blocking organelle clearance. A recent study reported that PLAAT1 promotes cardiolipin production in cultured cells, indicating a role in mitochondrial membrane lipid metabolism; however, its direct involvement in mitochondrial dynamics remains unclear. To address this, Sikder et al. (PLAAT1 expression triggers fragmentation of mitochondria in an enzyme activity-dependent manner. J Biochem 2023;175:101-13) established a doxycycline-inducible mouse PLAAT1 expression system in HEK293 cells. Catalytically active PLAAT1 rapidly induced mitochondrial fragmentation and peroxisome loss, independently of changes in Drp1, Mfn2 and Opa1 expression. These findings reveal a previously unrecognized role of PLAAT1 in regulating organelle dynamics and maintaining cellular homeostasis.