1. Golgi-derived PI ( 4 ) P-containing vesicles drive late steps of mitochondrial division.
- Author
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Nagashima S, Tábara LC, Tilokani L, Paupe V, Anand H, Pogson JH, Zunino R, McBride HM, and Prudent J
- Subjects
- 1-Phosphatidylinositol 4-Kinase genetics, 1-Phosphatidylinositol 4-Kinase metabolism, ADP-Ribosylation Factor 1 genetics, ADP-Ribosylation Factor 1 metabolism, Animals, COS Cells, Cell Line, Chlorocebus aethiops, Dynamins metabolism, Endoplasmic Reticulum metabolism, Endoplasmic Reticulum ultrastructure, HeLa Cells, Humans, Membrane Microdomains, Mitochondria ultrastructure, Mitochondrial Membranes metabolism, RNA Interference, Mitochondria metabolism, Mitochondrial Dynamics, Phosphatidylinositol Phosphates metabolism, trans-Golgi Network metabolism
- Abstract
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 guanosine triphosphatase 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., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2020
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