Gao Jieqiong, Franzkoch Rico, Rocha-Roa Cristian, Psathaki Olympia Ekaterini, Hensel Michael, Vanni Stefano, Ungermann Christian
Department of Biology/Chemistry, Biochemistry Section, Osnabrück University, Osnabrück, Germany.
Department of Biology/Chemistry, Division of Microbiology, Osnabrück University, Osnabrück, Germany.
J Cell Biol. 2025 Apr 7;224(4). doi: 10.1083/jcb.202410013. Epub 2025 Mar 6.
Endosomes are central organelles in the recycling and degradation of receptors and membrane proteins. Once endocytosed, such proteins are sorted at endosomes into intraluminal vesicles (ILVs). The resulting multivesicular bodies (MVBs) then fuse with the lysosomes, leading to the degradation of ILVs and recycling of the resulting monomers. However, the biogenesis of MVBs requires a constant lipid supply for efficient ILV formation. An ER-endosome membrane contact site has been suggested to play a critical role in MVB biogenesis. Here, we identify Any1 as a novel phospholipid scramblase, which functions with the lipid transfer protein Vps13 in MVB biogenesis. We uncover that Any1 cycles between the early endosomes and the Golgi and colocalizes with Vps13, possibly at a here-discovered potential contact site between lipid droplets (LDs) and endosomes. Strikingly, both Any1 and Vps13 are required for MVB formation, presumably to couple lipid flux with membrane homeostasis during ILV formation and endosome maturation.
内体是受体和膜蛋白循环利用及降解过程中的核心细胞器。一旦被内吞，此类蛋白在内体中被分选进入腔内小泡（ILV）。随后产生的多泡体（MVB）与溶酶体融合，导致ILV降解并使产生的单体得以循环利用。然而，MVB的生物发生需要持续的脂质供应以实现高效的ILV形成。内质网 - 内体膜接触位点被认为在MVB生物发生中起关键作用。在此，我们鉴定出Any1是一种新型磷脂翻转酶，它在MVB生物发生过程中与脂质转运蛋白Vps13协同发挥作用。我们发现Any1在早期内体和高尔基体之间循环，并与Vps13共定位，可能是在脂质滴（LD）与内体之间一个在此发现的潜在接触位点。引人注目的是，MVB形成需要Any1和Vps13两者，推测是为了在ILV形成和内体成熟过程中将脂质通量与膜稳态相耦合。
