细胞自噬及其调控病原真菌致病毒力的研究进展

Cell Autophagy and Its Effects on Regulating the Infection Process of Pathogenic Fungi

自噬是细胞通过自我降解、重新利用胞内蛋白质和细胞器的过程,有利于帮助生物体抵御饥饿或其他不良环境条件。以酵母等为对象的研究揭示细胞自噬可分为3种类型:巨自噬、微自噬以及分子伴侣介导的自噬,均具有重要的生理功能,其中针对巨自噬的机理研究最为深入广泛。不同自噬相关基因分别组成不同的功能模块,各自调控或完成自噬起始、自噬体形成、泛素化修饰和底物降解等。自噬活性的启动及不同底物的降解受表观遗传、转录、转录后及翻译后等多重调控。针对不同自噬相关基因功能的研究结果表明,不同病原真菌中存在与酵母自噬同源基因既保守又高度分化的生物学功能或效应。与酵母同源基因的生物学效应不同,不同关键自噬基因可分别参与调控病原真菌产孢、菌丝生长、细胞分化、侵染结构成熟,以及致病毒力等。自噬与致病毒力的关联性拓展了病原真菌致病机理的研究范畴,进一步研究病原菌自噬与寄主免疫互作的效应机制具有重要的生物学意义。

Cell autophagy is a process for degradation and recycle of cellular proteins and organelles against nutrient depletion or other adverse environments with essential physiological roles.Through the study on the model yeast species Saccharomyces cerevisiae,three types of cell autophagies,i.e.,macroautophagy,microautophagy and chaperon-mediated autophagy,have been characterized with particular functions.Among which,the processes of macroautophagy have been extensively studied that are generally referred to autophagy.It has been demonstrated that different autophagy-related genes can function together to form different modules to initiate cell autophagy,mediate autophagosome formation,control protein ubiquitination and substrate transportation and degradation.Due to the essential physiologies,cell autophagic activities are finely controlled by epigenetic,transcriptional,post-transcriptional,translational and post-translational factors.The yeast-like autophagy-related genes are conservatively present in different filamentous pathogenic fungi,however,both conserved and divergent functions have been reported for individual genes in different fungal pathogens.In particular,in contrast to some biological roles characterized in yeast cells,conserved autophagy core genes may be involved in the regulation of fungal conidiation,mycelial growth,cell differentiation,infection-structure differentiation and therefore the virulence of fungi against different hosts.These autophagy-related effects are not present in yeast.Overall,the connection of autophagy and fungal virulence well expand the investigation scope of fungal pathogenesis.Future efforts are still required to investigate if there is any involvement of autophagy with fungal immune evasion of hosts.