2026-01-09 東京大学
小胞体タンパク質PDZD8が持つ液体的性質が、小胞体とミトコンドリアを接触させる。
<関連情報>
- https://www.t.u-tokyo.ac.jp/press/pr2026-01-09-001
- https://www.t.u-tokyo.ac.jp/hubfs/press-release/2026/0109/001/text.pdf
- https://www.cell.com/molecular-cell/fulltext/S1097-2765(25)00980-3
膜タンパク質を介した相分離がオルガネラの接触部位を調整する Membrane-protein-mediated phase separation orchestrates organelle contact sites
Christian Hoffmann ∙ Takahiro Nagao ∙ Taka A. Tsunoyama ∙ … ∙ Akihiro Kusumi ∙ Yusuke Hirabayashi ∙ Dragomir Milovanovic
Molecular Cell Published:January 08, 2026
DOI:https://doi.org/10.1016/j.molcel.2025.12.006
Highlights
- Membrane-bound organelles form extensive, tightly apposed surfaces within cells
- PDZD8 phase separates at membrane contact sites via an intrinsically disordered region
- PDZD8 condensates mediate stable adhesion between ER and surrounding organelles
- These adhesions enable diffusion and enrichment of molecules within apposed organelles
Summary
Mitochondria and the endoplasmic reticulum (ER) contain large areas that are in close proximity. Yet the mechanism of how these inter-organellar adhesions are formed remains elusive. Tight functional connections, termed “membrane contact sites,” assemble at these areas and are essential for exchanging metabolites and lipids between the organelles. Recently, the ER-resident protein PDZ domain-containing protein 8 (PDZD8) was identified as a tether between the ER and mitochondria or late endosomes/lysosomes. Here, we show that PDZD8 can undergo phase separation via its intrinsically disordered region (IDR). Endogenously labeled PDZD8 forms condensates on membranes both in vitro and in mammalian cells. Electron microscopy analyses indicate that the expression of full-length PDZD8 rescues the decrease in inter-organelle contacts in PDZD8 knockout cells but not PDZD8 lacking its IDR. Together, this study identifies that PDZD8 condensates at the lipid interfaces act as an adhesive framework that stitches together the neighboring organelles and supports the structural and functional integrity of inter-organelle communication.
