Defective autophagy through epg5 mutation results in failure to reduce germ plasm and mitochondria
Defective autophagy through epg5 mutation results in failure to reduce germ plasm and mitochondria
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DOI：
10.1096/fj.14-265462
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发表时间：
2015-10-01
期刊：
影响因子：
4.8
通讯作者：
Schartl, Manfred
中科院分区：
文献类型：
--
作者：
Herpin, Amaury;Englberger, Eva;Schartl, Manfred
自噬是一种进化上保守的分解代谢过程，将细胞质成分转运到溶酶体进行降解。除了严格的应激反应诱导的自噬的经典观点，选择性编程的自噬最近报道的苍蝇和蠕虫的性腺发育的背景下，自噬似乎是必要的清除种质成分。类似的功能在脊椎动物中还没有被描述过。我们使用青鳉鱼来研究自噬在生殖腺形成和配子发生中的作用，这是第一次在脊椎动物生物体中进行，其生殖系是由种质指定的。使用转基因株系缺乏的Ol-epg 5基因-一个新的关键组成部分的自噬途径，我们表明，这种缺陷导致受损的自噬通量，可能归因于受损的成熟或处理的自噬体。ol-epg 5缺陷与选择性受损的精子发生和低等位基因传递率的突变等位基因所造成的失败的种质和线粒体清除过程中的生殖细胞特化和成年性腺。小鼠epg-5同源物在成熟和成年睾丸中表达相似，表明在脊椎动物精子发生过程中至少部分保守的功能。
Autophagy is an evolutionarily conserved catabolic process that transports cytoplasmic components to lysosomes for degradation. In addition to the canonical view of strict stress-response-induced autophagy, selectively programmed autophagy was recently reported in the context of gonad development of flies and worms, where autophagy seems to be necessary for clearance of germ plasm components. Similar functions have not been described in vertebrates. We used the medaka fish to study the role of autophagy in gonad formation and gametogenesis for the first time in a vertebrate organism for which thegermline is specifiedby germplasm. Using a transgenic line deficient in the Ol-epg5 gene-a new critical component of the autophagy pathway-we show that such deficiency leads to an impaired autophagic flux, possibly attributed to compromised maturation or processing of the autophagosomes. Ol-epg5 deficiency correlates with selectively impaired spermatogenesis and low allele transmission rates of the mutant allele caused by failure of germ plasm and mitochondria clearance during the process of germ cell specification and in the adult gonads. The mouse epg-5 homolog is similarly expressed in the maturating and adult testes, suggesting an at least partially conserved function of this process during spermatogenesis in vertebrates.