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Golgi-derived PI(4)P-containing vesicles drive late steps of mitochondrial division

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Science  20 Mar 2020:
Vol. 367, Issue 6484, pp. 1366-1371
DOI: 10.1126/science.aax6089

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PI(4)P regulates mitochondrial fission

Mitochondria are dynamic intracellular organelles, the shape and number of which are regulated by various cell-signaling pathways. Mitochondrial division is driven by the recruitment of a constricting guanosine triphosphatase protein at sites of contact with the endoplasmic reticulum, but other factors, including lysosomes, are also involved. Nagashima et al. now document an essential role for Golgi-derived vesicles bearing a specific lipid—phosphatidylinositol 4-phosphate, or PI(4)P—in the final steps of mitochondrial division. Disruption of PI(4)P production results in mitochondrial morphological defects indicative of an inability to complete fission.

Science, this issue p. 1366

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.

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