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Golgi derived PI(4)P-containing vesicle drives late steps of mitochondrial division

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Nagashima, Shun 
Tabara, Luis-Carlos 
Tilokani, Lisa 
Paupe, Vincent 
Anand, Hanish 


Mitochondrial plasticity is a key regulator of cell fate decisions. Mitochondrial division involves Dynamin-related protein-1 (Drp1) oligomerization, which constricts membranes at endoplasmic reticulum (ER) contact sites. The mechanisms driving the final steps of mitochondrial division are still unclear. Here, we found that microdomains of phosphatidylinositol 4-phosphate (PI(4)P) on Trans-Golgi network (TGN) vesicles were recruited to mitochondria-ER contact sites and could drive mitochondrial division downstream of Drp1. The loss of the small GTPase ADP-ribosylation factor 1 (Arf1) or its effector, phosphatidylinositol 4-kinase IIIβ (PI(4)KIIIβ) in different mammalian cell lines, prevented PI(4)P generation and led to a hyperfused and branched mitochondrial network, marked with extended mitochondrial constriction sites. Thus, recruitment of TGN-PI(4)P-containing vesicles at mitochondria-ER contact sites may trigger final events leading to mitochondrial scission.



1-Phosphatidylinositol 4-Kinase, ADP-Ribosylation Factor 1, Animals, COS Cells, Cell Line, Chlorocebus aethiops, Dynamins, Endoplasmic Reticulum, HeLa Cells, Humans, Membrane Microdomains, Mitochondria, Mitochondrial Dynamics, Mitochondrial Membranes, Phosphatidylinositol Phosphates, RNA Interference, trans-Golgi Network

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European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (749926)
Medical Research Council (MC_UU_00015/7)
MRC (1804261)
This work was supported by the Canadian Institutes of Health Research Operating Grants Program (CIHR grant 68833 to H.M.M.), the Medical Research Council (MRC grants MC_UU_00015/7 and RG89175 to J.P.), the Isaac Newton Trust (grant RG89529 to J.P.), and the Wellcome Trust Institutional Strategic Support Fund (grant RG89305 to J.P.). H.M.M. is a Canada Research Chair. S.N. and L.-C.T. are recipients of Daiichi Sankyo Foundation of Life Science and Ramon Areces postdoctoral fellowships, respectively. L.T. was supported by an MRC-funded graduate student fellowship. V.P was supported by the European Union’s Horizon 2020 research and innovation program (MITODYN-749926).