文章基本信息

标题：Septin 9 and phosphoinositides regulate lysosome localization and their association with lipid droplets
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作者：Pei Xuan Song ; Juan Peng ; Mohyeddine Omrane 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：5
页码：1-25
DOI：10.1016/j.isci.2022.104288
语种：English
出版社：Elsevier
摘要：SummaryThe 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.Graphical abstractDisplay OmittedHighlights•Septin 9 is regulates oleate-induced lysosome perinuclear clustering•Septin 9 and MTs regulate oleate-induced lysosome co-localization with Golgi•LDs with high septin 9 have less interaction with Rab7 and LAMP1•PIs have specific effects on LD and lysosomeCell biology; Organizational aspects of cell biology; Functional aspects of cell biology