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@ARTICLE{Hoffmann:283176,
author = {Hoffmann, Christian and Nagao, Takahiro and Tsunoyama, Taka
A and Tromm, Johannes Vincent and Logan, Chinyere and
Nakamura, Koki and Wang, Han and Bianchi, Frans and van den
Bogaart, Geert and Kusumi, Akihiro and Hirabayashi, Yusuke
and Milovanovic, Dragomir},
title = {{M}embrane-protein-mediated phase separation orchestrates
organelle contact sites.},
journal = {Molecular cell},
volume = {86},
number = {1},
issn = {1097-2765},
address = {[Cambridge, Mass.]},
publisher = {Cell Press},
reportid = {DZNE-2026-00055},
pages = {135 - 149.e9},
year = {2026},
abstract = {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.},
keywords = {Humans / Endoplasmic Reticulum: metabolism / Endoplasmic
Reticulum: ultrastructure / Endoplasmic Reticulum: genetics
/ Mitochondria: metabolism / Mitochondria: ultrastructure /
Mitochondria: genetics / Membrane Proteins: metabolism /
Membrane Proteins: genetics / Membrane Proteins: chemistry /
HeLa Cells / HEK293 Cells / Animals / Intrinsically
Disordered Proteins: metabolism / Intrinsically Disordered
Proteins: genetics / Biomolecular Condensates: metabolism /
Phase Separation / PDZD8 (Other) / biomolecular condensates
(Other) / endoplasmic reticulum (Other) / liquid-liquid
phase separation (Other) / membrane contact sites (Other) /
mitochondria (Other) / Membrane Proteins (NLM Chemicals) /
Intrinsically Disordered Proteins (NLM Chemicals)},
cin = {AG Milovanovic (Berlin)},
ddc = {610},
cid = {I:(DE-2719)1813002},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41512824},
doi = {10.1016/j.molcel.2025.12.006},
url = {https://pub.dzne.de/record/283176},
}