Abstract:
Mitochondria are maternally inherited, but the mechanisms underlying paternal mitochondrial elimination after fertilization are far less clear. Using Drosophila, we show that special egg-derived multivesicular body vesicles promote paternal mitochondrial elimination by activating an LC3-associated phagocytosis-like pathway, a cellular defense pathway commonly employed against invading microbes. Upon fertilization, these egg-derived vesicles form extended vesicular sheaths around the sperm flagellum, promoting degradation of the sperm mitochondrial derivative and plasma membrane. LC3-associated phagocytosis cascade of events, including recruitment of a Rubicon-based class III PI(3)K complex to the flagellum vesicular sheaths, its activation, and consequent recruitment of Atg8/LC3, are all required for paternal mitochondrial elimination. Finally, lysosomes fuse with strings of large vesicles derived from the flagellum vesicular sheaths and contain degrading fragments of the paternal mitochondrial derivative. Given reports showing that in some mammals, the paternal mitochondria are also decorated with Atg8/LC3 and surrounded by multivesicular bodies upon fertilization, our findings suggest that a similar pathway also mediates paternal mitochondrial elimination in other flagellated sperm-producing organisms.
摘要:
线粒体是母系遗传的,但是受精后父系线粒体消除的潜在机制远不清楚。用果蝇,我们表明,特殊的卵源多囊体囊泡通过激活LC3相关的吞噬作用样途径促进父系线粒体消除,通常用于抵抗入侵微生物的细胞防御途径。受精后,这些卵子来源的囊泡在精子鞭毛周围形成延伸的囊泡鞘,促进精子线粒体衍生物和质膜的降解。LC3相关吞噬级联事件,包括将基于Rubicon的III类PI(3)K复合物招募到鞭毛囊状鞘中,它的激活,以及随之而来的Atg8/LC3的募集,都是父系线粒体消除所必需的。最后,溶酶体与鞭毛囊泡鞘衍生的大囊泡融合,并含有父系线粒体衍生物的降解片段。鉴于报告显示,在一些哺乳动物中,父系线粒体也装饰有Atg8/LC3,受精后被多泡体包围,我们的研究结果表明,在其他有鞭毛的精子产生生物体中,类似的通路也介导父系线粒体的消除.