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

Jan Valečka; Voahirana Camosseto; David G McEwan; Seigo Terawaki; Zhuangzhuang Liu; Eva Strock; Catarina R Almeida; Bing Su; Ivan Dikic; Yinming Liang; Evelina Gatti; Philippe Pierre

doi:10.1098/rsos.202333

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

R Soc Open Sci. 2021 Jul 14;8(7):202333. doi: 10.1098/rsos.202333. eCollection 2021 Jul.

Authors

Jan Valečka¹, Voahirana Camosseto¹, David G McEwan², Seigo Terawaki³, Zhuangzhuang Liu⁴, Eva Strock¹, Catarina R Almeida⁵, Bing Su⁶, Ivan Dikic⁷, Yinming Liang⁴, Evelina Gatti^{1

5}, Philippe Pierre^{1

5

6}

Affiliations

¹ Aix Marseille Université, CNRS, INSERM, CIML, 13288 Marseille cedex 9, France.
² Tumour Cell Death Laboratory, Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
³ Department of Pathobiochemistry, Graduate School of Medicine, Osaka City University, Osaka, Japan.
⁴ School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, People's Republic of China.
⁵ Institute for Research in Biomedicine (iBiMED) and Ilidio Pinho Foundation, Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal.
⁶ Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
⁷ Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, 60590 Frankfurt (Main), Germany.

Abstract

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.

Keywords: LPS; RUFY; Skp; alveolar macrophages; mitophagy.

Associated data

figshare/10.6084/m9.figshare.c.5509720