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001     283176
005     20260129104043.0
024 7 _ |a 10.1016/j.molcel.2025.12.006
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024 7 _ |a 1097-2765
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037 _ _ |a DZNE-2026-00055
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100 1 _ |a Hoffmann, Christian
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245 _ _ |a Membrane-protein-mediated phase separation orchestrates organelle contact sites.
260 _ _ |a [Cambridge, Mass.]
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|b Cell Press
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520 _ _ |a 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.
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650 _ 7 |a PDZD8
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650 _ 7 |a biomolecular condensates
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650 _ 7 |a endoplasmic reticulum
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650 _ 7 |a liquid-liquid phase separation
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650 _ 7 |a membrane contact sites
|2 Other
650 _ 7 |a mitochondria
|2 Other
650 _ 7 |a Membrane Proteins
|2 NLM Chemicals
650 _ 7 |a Intrinsically Disordered Proteins
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Endoplasmic Reticulum: metabolism
|2 MeSH
650 _ 2 |a Endoplasmic Reticulum: ultrastructure
|2 MeSH
650 _ 2 |a Endoplasmic Reticulum: genetics
|2 MeSH
650 _ 2 |a Mitochondria: metabolism
|2 MeSH
650 _ 2 |a Mitochondria: ultrastructure
|2 MeSH
650 _ 2 |a Mitochondria: genetics
|2 MeSH
650 _ 2 |a Membrane Proteins: metabolism
|2 MeSH
650 _ 2 |a Membrane Proteins: genetics
|2 MeSH
650 _ 2 |a Membrane Proteins: chemistry
|2 MeSH
650 _ 2 |a HeLa Cells
|2 MeSH
650 _ 2 |a HEK293 Cells
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Intrinsically Disordered Proteins: metabolism
|2 MeSH
650 _ 2 |a Intrinsically Disordered Proteins: genetics
|2 MeSH
650 _ 2 |a Biomolecular Condensates: metabolism
|2 MeSH
650 _ 2 |a Phase Separation
|2 MeSH
700 1 _ |a Nagao, Takahiro
|b 1
700 1 _ |a Tsunoyama, Taka A
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700 1 _ |a Tromm, Johannes Vincent
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700 1 _ |a Logan, Chinyere
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700 1 _ |a Nakamura, Koki
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700 1 _ |a Wang, Han
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700 1 _ |a Bianchi, Frans
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700 1 _ |a van den Bogaart, Geert
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700 1 _ |a Kusumi, Akihiro
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700 1 _ |a Hirabayashi, Yusuke
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700 1 _ |a Milovanovic, Dragomir
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773 _ _ |a 10.1016/j.molcel.2025.12.006
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