英国剑桥大学Julien Prudent和加拿大麦吉尔大学Heidi M. McBride合作发现，高尔基来源的含PI(4)P的囊泡驱动线粒体分裂的后期步骤。该项研究成果发表在2020年3月20日出版的《科学》杂志上。

他们发现反式高尔基网络（TGN）囊泡上的磷脂酰肌醇4-磷酸[PI(4)P]的微区被募集到线粒体-内质网（ER）接触位点，并可能驱动动力蛋白相关蛋白1（Drp1）下游的线粒体分裂。

在不同的哺乳动物细胞系中，小鸟苷三磷酸酶ADP-核糖基化因子1（Arf1）或其效应物磷脂酰肌醇4激酶IIIβ[PI（4）KIIIβ]的丢失阻止了PI(4)P的产生，并导致过度融合和分支线粒体网络标记有扩展的线粒体收缩位点。

因此，在线粒体-ER接触位点募集含有TGN-PI(4)P的囊泡可能会触发导致线粒体分裂的最终事件。

研究人员表示，线粒体可塑性是决定细胞命运的关键因素。线粒体分裂涉及Drp1寡聚化，这会收缩ER接触位点的膜。线粒体分裂最终步骤的驱动机制仍不清楚。

附：英文原文

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

Author: Shun Nagashima, Luis-Carlos Tábara, Lisa Tilokani, Vincent Paupe, Hanish Anand, Joe H. Pogson, Rodolfo Zunino, Heidi M. McBride, Julien Prudent

Issue&Volume: 2020/03/20

Abstract: 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.

DOI: 10.1126/science.aax6089

Source: https://science.sciencemag.org/content/367/6484/1366