Golgi derived PI(4)P-containing vesicle drives late steps of mitochondrial division
| Autor: | Nagashima, Shun, Tabara, Luis-Carlos, Tilokani, Lisa, Paupe, Vincent, Anand, Hanish, Pogson, Joe H, Zunino, Rodolfo, McBride, Heidi M, Prudent, Julien |
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| Přispěvatelé: | Prudent, Julien [0000-0003-3821-6088], Apollo - University of Cambridge Repository |
| Rok vydání: | 2020 |
| Předmět: |
Dynamins
education Endoplasmic Reticulum Mitochondrial Dynamics Cell Line Mitochondria Membrane Microdomains Phosphatidylinositol Phosphates COS Cells Chlorocebus aethiops Mitochondrial Membranes Animals Humans ADP-Ribosylation Factor 1 RNA Interference 1-Phosphatidylinositol 4-Kinase health care economics and organizations HeLa Cells trans-Golgi Network |
| DOI: | 10.17863/cam.52765 |
| Popis: | 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. 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). |
| Databáze: | OpenAIRE |
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