When we get plump, so do the lipid storage droplets in our cells. By screening mutant yeast, Fei et al. identify the first gene that controls the size of these lipid droplets. A similar human gene is involved in a rare fat storage disorder.
Lipid droplets serve as containers for triacylglycerols and sterol esters. The structures might perform other functions as well, such as shuttling lipids between organelles and housing hydrophobic proteins. Wild-type budding yeast contain on average three to seven lipid droplets per cell, each somewhere between 0.5–1.5 μm in diameter. But how cells set the number and size of their lipid droplets is a mystery.
Fei et al. screened some 4,700 yeast mutants and identified 17 mutations that result in too few lipid droplets and more than 100 that result in too many. One gene, which the researchers dubbed FLD1, caught their attention because cells lacking it produced mammoth droplets 50 times the normal volume.
From in vitro and in vivo observations, the researchers discovered that the lipid droplets from the mutant yeast grow so large because they fuse promiscuously. It appears that FLD1 is involved in the synthesis of the phospholipids that encircle the droplets, as the FLD1 mutant yeast cells used shorter fatty acids to fashion these phospholipids. This effect might explain why the droplets can fuse more easily and thus can grow to monstrous proportions.
The human equivalent of FLD1, BSCL2, is defective in some forms of the rare Berardinelli-Seip congenital lipodystrophy, in which patients lack fat-storing adipocytes and often develop type II diabetes as teenagers. This connection might provide clues about how our bodies control fat production and storage.