%0 Journal Article
%A Furthmann, Nikolas
%A Bader, Verian
%A Angersbach, Lena
%A Blusch, Alina
%A Goel, Simran
%A Sánchez-Vicente, Ana
%A Krause, Laura J.
%A Chaban, Sarah A.
%A Grover, Prerna
%A Trinkaus, Victoria A.
%A van Well, Eva M.
%A Jaugstetter, Maximilian
%A Tschulik, Kristina
%A Damgaard, Rune Busk
%A Saft, Carsten
%A Ellrichmann, Gisa
%A Gold, Ralf
%A Koch, Arend
%A Englert, Benjamin
%A Westenberger, Ana
%A Klein, Christine
%A Jungbluth, Lisa
%A Sachse, Carsten
%A Behrends, Christian
%A Glatzel, Markus
%A Hartl, F. Ulrich
%A Nakamura, Ken
%A Christine, Chadwick W.
%A Huang, Eric J.
%A Tatzelt, Jörg
%A Winklhofer, Konstanze F.
%T NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62
%J Nature Communications
%V 14
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M FZJ-2024-00271
%P 8368
%D 2023
%X NEMO is a ubiquitin-binding protein which regulates canonical NF-κB pathwayactivation in innate immune signaling, cell death regulation and host-pathogeninteractions. Here we identify an NF-κB-independent function of NEMO inproteostasis regulation by promoting autophagosomal clearance of proteinaggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxicstress and are vulnerable to proteostasis challenges. Moreover, apatient with a mutation in the NEMO-encoding IKBKG gene resulting indefective binding of NEMO to linear ubiquitin chains, developed a widespreadmixed brain proteinopathy, including α-synuclein, tau and TDP-43 pathology.NEMO amplifies linear ubiquitylation at α-synuclein aggregates and promotesthe local concentration of p62 into foci. In vitro, NEMO lowers the thresholdconcentrations required for ubiquitin-dependent phase transition of p62. Insummary, NEMO reshapes the aggregate surface for efficient autophagosomalclearancebyprovidingamobilephase at theaggregate interphase favoringcocondensationwith p62.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 38114471
%U <Go to ISI:>//WOS:001131904500002
%R 10.1038/s41467-023-44033-0
%U https://juser.fz-juelich.de/record/1020576