Torres-Romero Ismael, Légeret Bertrand, Bertrand Marie, Sorigue Damien, Damm Alicia, Cuiné Stéphan, Veillet Florian, Blot Carla, Brugière Sabine, Couté Yohann, Garneau Matthew G, Kotapati Hari K, Xin Yi, Xu Jian, Bates Philip D, Thiam Abdou R, Beisson Fred, Li-Beisson Yonghua
Aix Marseille Univ, CEA, CNRS, Institute of Bioscience and Biotechnology of Aix Marseille, BIAM, Saint-Paul-Lez-Durance 13108, France.
Laboratoire de Physique de l'École Normale Supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université de Paris Cité, Paris 75005, France.
Natl Sci Rev. 2024 Nov 7;11(12):nwae398. doi: 10.1093/nsr/nwae398. eCollection 2024 Dec.
Lipid droplets (LDs) are the major sites of lipid and energy homeostasis. However, few LD biogenesis proteins have been identified. Using model microalga , 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--trimethylhomoserine (DGTS). Over-expression of increased LD abundance and boosted TAG content. Purified recombinant ABHD1 hydrolyzed lyso-DGTS, producing a free fatty acid and a glyceryltrimethylhomoserine. 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.
脂滴（LDs）是脂质和能量稳态的主要场所。然而，已鉴定出的参与脂滴生物合成的蛋白质很少。利用模式微藻，我们发现ABHD1，一种含有α/β水解酶结构域的蛋白质，定位于脂滴表面，并通过两种作用刺激脂滴形成：一种是酶促作用，另一种是结构作用。基因敲除突变体含有相似量的三酰甘油（TAG），但其脂滴显示出较高含量的甜菜碱脂质二酰甘油 - 三甲基高丝氨酸（DGTS）的溶血衍生物。ABHD1的过表达增加了脂滴丰度并提高了TAG含量。纯化的重组ABHD1水解溶血DGTS，产生游离脂肪酸和甘油基三甲基高丝氨酸。嵌入脂滴的囊泡表明ABHD1促进了脂滴的出现。综上所述，这些结果通过其对溶血DGTS的脂肪酶活性及其独特的生物物理特性，将ABHD1确定为脂滴形成中的一个新参与者。这项研究进一步表明，靶向脂滴并能够作用于其极性脂质外壳的脂肪酶可能是促进真核细胞中脂滴组装的有趣工具。
