α/β hydrolase domain-containing protein 1 acts as a lysolipid lipase and is involved in lipid droplet formation.

Abstract

Lipid droplets (LDs) are the major sites of lipid and energy homeostasis. However, few LD biogenesis proteins have been identified. Using model microalga Chlamydomonas, we show that ABHD1, an α/β-hydrolase domain-containing protein, is localized to the LD surface and stimulates LD formation through two actions: one enzymatic and one structural. The knockout mutants contained similar amounts of triacylglycerols (TAG) but their LDs showed a higher content of lyso-derivatives of betaine lipid diacylglyceryl-N,N,N-trimethylhomoserine (DGTS). Over-expression of ABHD1 increased LD abundance and boosted TAG content. Purified recombinant ABHD1 hydrolyzed lyso-DGTS, producing a free fatty acid and a glyceryltrimethylhomoserine. In vitro droplet-embedded vesicles showed that ABHD1 promoted LD emergence. Taken together, these results identify ABHD1 as a new player in LD formation by its lipase activity on lyso-DGTS and by its distinct biophysical property. This study further suggests that lipases targeted to LDs and able to act on their polar lipid coat may be interesting tools to promote LD assembly in eukaryotic cells.