Zhixiao Wu, Lena A Berlemann, Verian Bader, Dominik A Sehr, Eva Dawin, Alberto Covallero, Jens Meschede, Lena Angersbach, Cathrin Showkat, Jonas B Michaelis, Christian Münch, Bettina Rieger, Dmitry Namgaladze, Maria Georgina Herrera, Fabienne C Fiesel, Wolfdieter Springer, Marta Mendes, Jennifer Stepien, Katalin Barkovits, Katrin Marcus, Albert Sickmann, Gunnar Dittmar, Karin B Busch, Dietmar Riedel, Marisa Brini, Jörg Tatzelt, Tito Cali, Konstanze F Winklhofer
Mitochondria are increasingly recognized as cellular hubs to orchestrate signaling pathways that regulate metabolism, redox homeostasis, and cell fate decisions. Recent research revealed a role of mitochondria also in innate immune signaling; however, the mechanisms of how mitochondria affect signal transduction are poorly understood. Here, we show that the NF-κB pathway activated by TNF employs mitochondria as a platform for signal amplification and shuttling of activated NF-κB to the nucleus. TNF treatment induces the recruitment of HOIP, the catalytic component of the linear ubiquitin chain assembly complex (LUBAC), and its substrate NEMO to the outer mitochondrial membrane, where M1- and K63-linked ubiquitin chains are generated...
December 15, 2022: EMBO Journal