Amado Lucía, Percifull Louis, Franzkoch Rico, Flatemersch Vico, Brüggemann Eleni Joana, Psathaki Olympia Ekaterini, Schuldiner Maya, Bohnert Maria, Bülow Margret H, González Montoro Ayelén
Cellular Communication Laboratory, Department of Biology/Chemistry, Osnabrück University, Barbarastrasse 13, 49076, Osnabrück, Germany.
Institute of Cell Dynamics and Imaging, University of Münster, Von-Esmarch-Str. 56, 48149, Münster, Germany.
Sci Rep. 2025 Jul 8;15(1):24480. doi: 10.1038/s41598-025-07934-2.
Peroxisomes are ubiquitous organelles that mediate central metabolic functions, such as fatty acid β-oxidation, as well as diverse tissue- and organism-specific processes. Membrane contact sites, regions of close apposition with other organelles for direct communication, are central to several aspects of their life cycle. Pex3 is a conserved multifunctional peroxisomal transmembrane protein that is involved in the insertion of peroxisomal membrane proteins, in pexophagy, and in the formation of membrane contact sites. Here, we show that high Pex3 levels in Saccharomyces cerevisiae induce the formation of peroxisome clusters surrounded by lipid droplets, mediated by peroxisome-peroxisome and peroxisome-lipid droplet contact sites. This clustering occurs independently of Pex3 partners in other processes Pex19, Inp1, and Atg36. The cytosolic domain of Pex3 binds peroxisomes, suggesting a direct role in homotypic contact site formation. Lipid droplet-peroxisome contact sites require the lipid droplet-localized triacylglycerol lipase Tgl4, which is enriched at this interface along with other lipases. Pex3 overexpression in Drosophila melanogaster similarly alters peroxisome and lipid droplet morphology and promotes contact site formation. Together, our results offer novel molecular insights into homotypic peroxisome contact sites and peroxisome-lipid droplet contact sites across species.
过氧化物酶体是普遍存在的细胞器，介导诸如脂肪酸β-氧化等核心代谢功能以及多种组织和生物体特异性过程。膜接触位点是与其他细胞器紧密并列以进行直接通讯的区域，在其生命周期的几个方面起着核心作用。Pex3是一种保守的多功能过氧化物酶体跨膜蛋白，参与过氧化物酶体膜蛋白的插入、过氧化物酶体自噬以及膜接触位点的形成。在这里，我们表明酿酒酵母中高水平的Pex3会诱导形成被脂滴包围的过氧化物酶体簇，这是由过氧化物酶体-过氧化物酶体和过氧化物酶体-脂滴接触位点介导的。这种聚集独立于Pex3在其他过程中的伙伴Pex19、Inp1和Atg36发生。Pex3的胞质结构域与过氧化物酶体结合，表明其在同型接触位点形成中起直接作用。脂滴-过氧化物酶体接触位点需要脂滴定位的三酰甘油脂肪酶Tgl4，它与其他脂肪酶一起在这个界面富集。果蝇中Pex3的过表达同样会改变过氧化物酶体和脂滴的形态并促进接触位点的形成。总之，我们的结果为跨物种的同型过氧化物酶体接触位点和过氧化物酶体-脂滴接触位点提供了新的分子见解。
