TY - JOUR A1 - Valečka, Jan A1 - Camosseto, Voahirana A1 - McEwan, David G. A1 - Liu, Zhuangzhuang A1 - Strock, Eva A1 - Almeida, Catarina R. A1 - Su, Bing A1 - Đikić, Ivan A1 - Liang, Yinming A1 - Gatti, Evelina A1 - Pierre, Philippe T1 - RUFY4 exists as two translationally regulated isoforms, that localize to the mitochondrion in activated macrophages T2 - Royal Society Open Science N2 - We report here that RUFY4, a newly characterized member of the ‘RUN and FYVE domain-containing’ family of proteins previously associated with autophagy enhancement, is highly expressed in alveolar macrophages (AM). We show that RUFY4 interacts with mitochondria upon stimulation by microbial-associated molecular patterns of AM and dendritic cells. RUFY4 interaction with mitochondria and other organelles is dependent on a previously uncharacterized OmpH domain located immediately upstream of its C-terminal FYVE domain. Further, we demonstrate that rufy4 messenger RNA can be translated from an alternative translation initiation codon, giving rise to a N-terminally truncated form of the molecule lacking most of its RUN domain and with enhanced potential for its interaction with mitochondria. Our observations point towards a role of RUFY4 in selective mitochondria clearance in activated phagocytes. KW - RUFY KW - mitophagy KW - Skp KW - alveolar macrophages KW - LPS Y1 - 2021 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62916 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-629166 SN - 2054-5703 N1 - The project and J.V. were supported by grants from l'Agence Nationale de la Recherche (ANR) ‘DCBIOL Labex ANR-11-LABEX-0043’, ‘INFORM Labex ANR-11-LABEX-0054’ funded by the ‘Investissements d'Avenir’ French government programme. This work was also financially supported by the project PTDC/BIA-CEL/28791/2017 and POCI-01-0145-FEDER-028791, as well as POCI-01-0145-FEDER-030882 and PTDC/BIA-MOL/30882/2017, funded by FEDER, through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI), and by national funds (OE), through FCT/MCTES. N1 - Data accessibility The MS proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD026728. N1 - Electronic supplementary material is available online at https://doi.org/10.6084/m9.figshare.c.5509720. VL - 8 IS - 7 SP - 1 EP - 15 PB - Royal Soc. Publ. CY - London ER -