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在顶头孢霉中选择性自噬相关基因 Acatg11 的功能分析。

Functional analysis of the selective autophagy related gene Acatg11 in Acremonium chrysogenum.

机构信息

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Fungal Genet Biol. 2017 Oct;107:67-76. doi: 10.1016/j.fgb.2017.08.006. Epub 2017 Aug 19.

DOI:10.1016/j.fgb.2017.08.006
PMID:28830792
Abstract

Autophagy is a highly conserved degradation system in eukaryotes. Selective autophagy is used for the degradation of selective cargoes. Selective autophagic processes of yeast include pexophagy, mitophagy, and cytoplasm-to-vacuole targeting (Cvt) pathway in which particular vacuolar proteins, such asaminopeptidase I (Ape1), are selectively transported to vacuoles. However, the physiological role of selective autophagy remains elusive in filamentous fungi. ATG11 family proteins asa basic scaffold are essential for most selective autophagy pathways in yeast. Here, Acatg11, encoding a putative ATG11 family protein, was identified and cloned from the cephalosporin producing strain Acremonium chrysogenum based on the sequence similarity of ATG11 superfamily proteins. Disruption of Acatg11 inhibited the maturation of preApe1 during fermentation indicating that Acatg11 is involved in Cvt pathway. In addition, pexophagy and mitophagy were blocked in the Acatg11 disruption mutant (ΔAcatg11). Intriguingly, the nonselective autophagy was deficient in ΔAcatg11 under starvation induction or during fermentation. Disruption of Acatg11 significantly enhanced fungal conidiation, but reduced cephalosporin production. These results indicated that Acatg11 is required for both selective and nonselective autophagy during fermentation and has a strong impact on morphological differentiation and cephalosporin production of A. chrysogenum.

摘要

自噬是真核生物中高度保守的降解系统。选择性自噬用于降解选择性货物。酵母的选择性自噬过程包括pexophagy、mitophagy 和细胞质到液泡靶向(Cvt)途径,其中特定的液泡蛋白,如氨基肽酶 I(Ape1),被选择性地运输到液泡中。然而,丝状真菌中选择性自噬的生理作用仍然难以捉摸。ATG11 家族蛋白作为基本支架对于酵母中的大多数选择性自噬途径都是必不可少的。在这里,根据 ATG11 超家族蛋白的序列相似性,从头孢菌素产生菌株顶头孢霉(Acremonium chrysogenum)中鉴定并克隆了 Acatg11,它编码一个假定的 ATG11 家族蛋白。Acatg11 的破坏抑制了发酵过程中 preApe1 的成熟,表明 Acatg11 参与了 Cvt 途径。此外,pexophagy 和 mitophagy 在 Acatg11 破坏突变体(ΔAcatg11)中被阻断。有趣的是,在饥饿诱导或发酵过程中,ΔAcatg11 中的非选择性自噬不足。Acatg11 的破坏显著增强了真菌分生孢子的形成,但降低了头孢菌素的产生。这些结果表明,Acatg11 在发酵过程中既需要选择性自噬,也需要非选择性自噬,并且对顶头孢霉的形态分化和头孢菌素的产生有很大的影响。

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