RUFY4 exists as two translationally regulated isoforms, that localize to the mitochondrion in activated macrophages

  • 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.

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Author:Jan Valečka, Voahirana CamossetoORCiD, David G. McEwanORCiD, Zhuangzhuang Liu, Eva Strock, Catarina R. AlmeidaORCiD, Bing Su, Ivan ĐikićORCiDGND, Yinming Liang, Evelina GattiORCiD, Philippe PierreORCiD
URN:urn:nbn:de:hebis:30:3-629166
DOI:https://doi.org/10.1098/rsos.202333
ISSN:2054-5703
Parent Title (English):Royal Society Open Science
Publisher:Royal Soc. Publ.
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2021/07/14
Date of first Publication:2021/07/14
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/06/14
Tag:LPS; RUFY; Skp; alveolar macrophages; mitophagy
Volume:8
Issue:7
Page Number:15
First Page:1
Last Page:15
Note:
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.
Note:
Data accessibility
The MS proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD026728.
Note:
Electronic supplementary material is available online at https://doi.org/10.6084/m9.figshare.c.5509720.
HeBIS-PPN:510041442
Institutes:Medizin / Medizin
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International