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

Jan Valečka (1) , Voahirana Camosseto (1) , David Mcewan (2) , Seigo Terawaki (3) , Zhuangzhuang Liu (4) , Eva Strock (1) , Catarina Almeida (5) , Bing Su (6) , Ivan Dikic (7) , Yinming Liang (4) , Evelina Gatti (1) , Philippe Pierre (1)

1 CIML - Centre d'Immunologie de Marseille - Luminy
2 The Beatson Institute for Cancer Research
3 OCU - Osaka City University
4 Xinxiang Medical University
5 iBiMED - Institute for Research in Biomedicine
6 Shangaï Jiao Tong University [Shangaï]
7 Université Johann Wolfgang Goethe de Francfort-sur-le-Main

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: RUFY; mitophagy; Skp; alveolar macrophages; LPS

Domains: Life Sciences [q-bio]

Jan Valečka, Voahirana Camosseto, David Mcewan, Seigo Terawaki, Zhuangzhuang Liu, et al.. RUFY4 exists as two translationally regulated isoforms, that localize to the mitochondrion in activated macrophages. Royal Society Open Science, 2021, 8 (7), pp.202333. ⟨10.1098/rsos.202333⟩. ⟨hal-03374685⟩