Septin 9 and phosphoinositides regulate lysosome localization and their association with lipid droplets

iScience

Ting ting Cai¹  Ama Gassama-Diagne¹  Juan Peng¹  Pei Xuan Song²  Mohyeddine Omrane²  Didier Samuel² 

[1] UMR-S 1193, Université Paris-Saclay, 94800 Villejuif, France;Unité 1193, INSERM, 94800 Villejuif, France;

关键词: Cell biology;    Organizational aspects of cell biology;    Functional aspects of cell biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown