Arumugam Balasubramanian, Alan Y Hsu, Laxman Ghimire, Muhammad Tahir, Pascal Devant, Pietro Fontana, Gang Du, Xing Liu, Dang Fabin, Hiroto Kambara, Xuemei Xie, Fei Liu, Tomoya Hasegawa, Rong Xu, Hongbo Yu, Mei Chen, Steven Kolakowski, Sunia Trauger, Martin Røssel Larsen, Wenyi Wei, Hao Wu, Jonathan C Kagan, Judy Lieberman, Hongbo R Luo
Plasma membrane perforation elicited by caspase cleavage of the gasdermin D (GSDMD) N-terminal domain (GSDMD-NT) triggers pyroptosis. The mechanisms underlying GSDMD membrane translocation and pore formation are not fully understood. Here, using a proteomics approach, we identified fatty acid synthase (FASN) as a GSDMD-binding partner. S-palmitoylation of GSDMD at Cys191/192 (human/mouse), catalyzed by palmitoyl acyltransferases ZDHHC5 and ZDHHC9 and facilitated by reactive oxygen species (ROS), directly mediated membrane translocation of GSDMD-NT but not full-length GSDMD (GSDMD-FL)...
March 26, 2024: Science Immunology