Song Pei Xuan, Peng Juan, Omrane Mohyeddine, Cai Ting Ting, Samuel Didier, Gassama-Diagne Ama
Unité 1193, INSERM, 94800 Villejuif, France.
UMR-S 1193, Université Paris-Saclay, 94800 Villejuif, France.
iScience. 2022 Apr 25;25(5):104288. doi: 10.1016/j.isci.2022.104288. eCollection 2022 May 20.
The accumulation of lipid droplets (LDs) in the liver is a hallmark of steatosis, which is often associated with lysosomal dysfunction. Nevertheless, the underlying mechanisms remain unclear. Here, using Huh7 cells loaded with oleate as a model to study LD metabolism, we show that cellular content and distribution of LDs are correlated with those of the lysosome and regulated by oleate and septin 9. High expression of septin 9 promotes perinuclear clustering of lysosomes which co-localized with Golgi and not with their surrounding LDs. On the other hand, knockdown of septin 9 disperses the two organelles which colocalize at the cell periphery. The Rab7 is present around these peripheral LDs. PtdIns5P which binds septin 9 and MTMR3 which converts PtdIns(3,5)P2 into PtdIns(5) recapitulates the effects of septin 9. By contrast, PtdIns(3,5)P2 promotes LD/lysosome co-localization. Overall, our data reveal a phosphoinositide/septin 9-dependent mechanism that regulates LD behavior through the control of their association with lysosomes.
肝脏中脂滴（LDs）的积累是脂肪变性的一个标志，脂肪变性通常与溶酶体功能障碍有关。然而，其潜在机制仍不清楚。在这里，我们以加载油酸的Huh7细胞作为研究LD代谢的模型，表明LDs的细胞含量和分布与溶酶体的相关，并受油酸和septin 9的调节。septin 9的高表达促进了与高尔基体共定位而非与其周围LDs共定位的溶酶体的核周聚集。另一方面，敲低septin 9会使这两种细胞器分散，它们在细胞周边共定位。Rab7存在于这些周边的LDs周围。与septin 9结合的PtdIns5P和将PtdIns(3,5)P2转化为PtdIns(5)的MTMR3重现了septin 9的作用。相比之下，PtdIns(3,5)P2促进LD/溶酶体共定位。总体而言，我们的数据揭示了一种磷酸肌醇/septin 9依赖性机制，该机制通过控制LDs与溶酶体的关联来调节LD行为。
