Investigating lipid droplets biogenesis: the role of CtBP1/BARS

Lipid droplets (LDs) are intracellular lipid-storing organelles surrounded by a phospholipid monolayer. LDs emerge as metabolically active organelles involved in many biological processes and linked to the pathogenesis of various metabolic diseases. The mechanism underlying LD formation is still poorly understood and the molecular players that take part in this process have to be identified. Here, we provide evidence that a member of the C-terminal binding protein (CtBP) family, CtBP1/BARS (for brevity BARS), associates with LDs and is required for their formation. BARS is a fission-inducing protein that regulates several membrane trafficking events. Since the widely accepted model regarding LD biogenesis describes the formation of these organelles as fission products of the endoplasmic reticulum, we wondered whether BARS could play a role in this process. Interestingly, we show that BARS depletion/inhibition dramatically reduces the LD number, while its over-expression/activation increases LD formation in oleate-treated HeLa cells. These findings suggest a central role of BARS in LD formation. Furthermore, we found that BARS interacts with Acyl-CoA:lysocardiolipin acyltransferase (LCLAT1/AGPAT8) that catalyses acylation of lysophosphatidilinositol (LPI) to phosphatidylinositol (PI), one of the main LD surface phospholipid. Intriguingly, BARS and AGPAT8 are both recruited and co-localize on LDs. Future studies will elucidate the physiological relevance of the interaction BARS-AGPAT8 in LD biogenesis.