Instituto de Bioquimica Médica Leoplodo de Meis, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, cep 21941-902, Rio de Janeiro, Rio de Janeiro Brazil.
FEMS Yeast Res. 2019 May 1;19(3). doi: 10.1093/femsyr/foz030.
In this study, we found that cell cycle arrest induced by alpha-factor mating pheromone (G1), hydroxyurea (S) or nocodazole (G2/M) was associated to increased lipid droplet (LD) content. To identify novel cell cycle genes involved in LD homeostasis, we screened a deletion library for strains with altered LD levels. Among the mutants related to mitotic cell cycle, we found 24 hits that displayed a significantly higher LD content. Ontology mapping showed that neither a biological process nor a specific cell cycle phase was enriched among the hits. We decided to further study the role of SWI4 on LD homeostasis as it is involved in G1/S transition, a stage where lipolysis is active. The high LD content of swi4Δ mutant was not due to inhibition of lipolysis, but due to an increase in triacylglycerol (TAG) synthesis. In addition, deletion of the AMP kinase gene SNF1 or inhibition of TORC1 activity, both known regulators of LD homeostasis, further increased the LD content of a swi4Δ mutant. These findings highlight a role of the cell cycle regulator SWI4 in the coordination of lipid metabolism which is independent of the TORC1 and SNF1/AMPK pathways.
在这项研究中，我们发现α-因子交配信息素（G1）、羟基脲（S）或诺考达唑（G2/M）诱导的细胞周期停滞与脂滴（LD）含量的增加有关。为了鉴定参与 LD 动态平衡的新的细胞周期基因，我们筛选了一个缺失文库，以寻找 LD 水平改变的菌株。在与有丝分裂细胞周期相关的突变体中，我们发现有 24 个突变体显示出明显更高的 LD 含量。本体论映射表明，在这些突变体中，既没有生物过程也没有特定的细胞周期阶段富集。我们决定进一步研究 SWI4 在 LD 动态平衡中的作用，因为它参与 G1/S 转换，这是脂肪分解活跃的阶段。swi4Δ 突变体的高 LD 含量不是由于脂肪分解的抑制，而是由于三酰基甘油 (TAG) 合成的增加。此外，AMP 激酶基因 SNF1 的缺失或 TORC1 活性的抑制，这两者都是 LD 动态平衡的已知调节剂，进一步增加了 swi4Δ 突变体的 LD 含量。这些发现强调了细胞周期调节剂 SWI4 在协调脂代谢中的作用，这与 TORC1 和 SNF1/AMPK 途径无关。
