PT - JOURNAL ARTICLE AU - Yan Li AU - Siwei Huang AU - Xuesong Li AU - Xingyu Yang AU - Ningyi Xu AU - Jianan Qu AU - Ho Yi Mak TI - The endoplasmic reticulum-resident protein TMEM-120/TMEM120A promotes fat storage in <em>C. elegans</em> and mammalian cells AID - 10.1101/2021.06.29.450322 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.06.29.450322 4099 - http://biorxiv.org/content/early/2021/06/29/2021.06.29.450322.short 4100 - http://biorxiv.org/content/early/2021/06/29/2021.06.29.450322.full AB - The synthesis of triacylglycerol (TAG) is essential for the storage of excess fatty acids, which can subsequently be used for energy or cell growth. A series of enzymes act in the endoplasmic reticulum (ER) to synthesize TAG, prior to its transfer to lipid droplets (LDs), which are conserved organelles for fat storage. Here, we report that the deficiency of TMEM-120/TMEM120A, a protein with 6-transmembrane helices, retards TAG synthesis and LD expansion in C. elegans. GFP fusion proteins of TMEM-120, expressed at the endogenous level in live worms, were observed throughout the ER network. Using Stimulated Raman Scattering, we demonstrated the specific requirement of TMEM-120 in the storage of exogenous fatty acids in LDs. Knockdown of TMEM120A impedes adipogenesis of pre-adipocytes in vitro, while its over-expression is sufficient to promote LD expansion in mammalian cells. Our results suggest that TMEM-120/TMEM120A plays a conserved role in increasing the efficiency of TAG synthesis.Competing Interest StatementThe authors have declared no competing interest.