Phosphatidic acid (PA) is the simplest cellular glycerophospholipid characterized by unique biophysical properties: a small headgroup; negative charge; and a phosphomonoester group. Upon interaction with lysine or arginine, PA charge increases from −1 to −2 and this change stabilizes protein–lipid interactions. The biochemical properties of PA also allow interactions with lipids in several subcellular compartments. Based on this feature, PA is involved in the regulation and amplification of many cellular signalling pathways and functions, as well as in membrane rearrangements. Thereby, PA can influence membrane fusion and fission through four main mechanisms: it is a substrate for enzymes producing lipids (lysophosphatidic acid and diacylglycerol) that are involved in fission or fusion; it contributes to membrane rearrangements by generating negative membrane curvature; it interacts with proteins required for membrane fusion and fission; and it activates enzymes whose products are involved in membrane rearrangements. Here, we discuss the biophysical properties of PA in the context of the above four roles of PA in membrane fusion and fission.

Membrane fission is an essential cellular process by which continuous membranes split into separate parts. We have previously identified CtBP1-S/BARS (BARS) as a key component of a protein complex that is required for fission of several endomembranes, including basolateral post-Golgi transport carriers. Assembly of this complex occurs at the Golgi apparatus, where BARS binds to the phosphoinositide kinase PI4KIIIβ through a 14-3-3γ dimer, as well as to ARF and the PKD and PAK kinases. We now report that, when incorporated into this complex, BARS binds to and activates a trans-Golgi lysophosphatidic acid (LPA) acyltransferase type δ (LPAATδ) that converts LPA into phosphatidic acid (PA); and that this reaction is essential for fission of the carriers. LPA and PA have unique biophysical properties, and their interconversion might facilitate the fission process either directly or indirectly (via recruitment of proteins that bind to PA, including BARS itself).

Renard et al. (2018) suggested to classify membrane fission mechanisms into two main categories: active fission (with the direct consumption of cellular energy by nucleoside triphosphate hydrolysis) and passive fission (without the direct use of energy). Many membrane fission processes are dependent on the interaction of fission-inducing proteins with specific lipid molecules (see below). In some cases, passive fission might be energized indirectly, via the energy used in the synthesis of these lipid cofactors (Gopaldass et al., 2017). Moreover, membrane fission processes can be classified into two types: "normal topology fission" (membrane-enclosed compartments bud toward the cytosol) and "reverse topology fission" (membrane-enclosed compartments bud away from the cytosol) (