Cellular autophagy: surrender, avoidance and subversion by microorganisms.
Cellular autophagy: surrender, avoidance and subversion by microorganisms.
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DOI：
10.1038/nrmicro865
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发表时间：
2004-04
期刊：
影响因子：
--
通讯作者：
Jackson WT
中科院分区：
文献类型：
--
作者：
Kirkegaard K;Taylor MP;Jackson WT
自噬是一种进化上保守的细胞过程，由饥饿和其他发育和环境线索启动。自噬体的形成和成熟涉及胞质在双膜结合囊泡内的隔离，并导致胞质内容物的蛋白酶体非依赖性降解。 许多自噬所需的基因已经被鉴定出来，首先是在酿酒酵母中，然后通过同源性在其他生物中。 已经开发了许多用于自噬的显微镜、药理学和生物化学测定。对自噬所需基因的鉴定现在允许对自噬在感兴趣的过程中的参与进行遗传测试。 一些入侵的细菌物种很容易被自噬破坏。然而，有人认为嗜肺军团菌和其他几种细菌可以破坏自噬成分，以促进其生长。 抗病毒蛋白PKR激活的后果之一是细胞自噬的增加，这使得自噬可能是细胞抗病毒反应的一个组成部分。然而，几种正链RNA病毒在双膜结合囊泡上复制它们的基因组，这些囊泡被认为来自自噬结构。 至于其他针对微生物的细胞防御，一些细菌和病毒似乎已经进化出抑制或破坏自噬的机制。细胞内的细菌和病毒必须在宿主强烈的抗菌反应中存活下来才能成功复制。自噬的细胞过程--由双膜结合的隔室吞噬部分细胞质，然后成熟降解其细胞质内容物--可能就是这样一种宿主细胞反应。一些证据表明，细菌和病毒都容易受到自噬破坏，成功的病原体已经进化出避免自噬的策略，或者主动破坏其成分，以促进自身的复制。微生物避免和破坏自噬的分子机制将是未来许多研究的主题，不仅要研究它们在这些微生物复制中的作用，而且还因为它们将提供-正如细菌和病毒经常拥有的-独特的工具来研究细胞过程本身。
Autophagy is an evolutionarily conserved cellular process that is initiated by starvation and other developmental and environmental cues. The formation and maturation of autophagosomes involves the sequestration of cytoplasm within double-membrane-bound vesicles and leads to proteasome-independent degradation of the cytosolic contents. Many genes that are required for autophagy have been identified, first in the yeast Saccharomyces cerevisiae, and then in other organisms by homology. Numerous microscopical, pharmacological and biochemical assays for autophagy have been developed. The identification of genes that are required for autophagy now allows genetic tests for the involvement of autophagy in a process of interest. Several invasive bacterial species are vulnerable to destruction by autophagy. However, it has been argued that Legionella pneumophila and several other bacterial species can subvert autophagic components to enhance their growth. One of the consequences of the activation of the antiviral protein PKR is an increase in cellular autophagy, which makes it likely that autophagy is a component of the cellular antiviral response. However, several positive-strand RNA viruses replicate their genomes on double-membrane-bound vesicles that are thought to be derived from autophagic structures. As for other cellular defences against microorganisms, some bacteria and viruses seem to have evolved mechanisms to inhibit or subvert autophagy. Intracellular bacteria and viruses must survive the vigorous antimicrobial responses of their hosts to replicate successfully. The cellular process of autophagy — in which compartments bound by double membranes engulf portions of the cytosol and then mature to degrade their cytoplasmic contents — is likely to be one such host-cell response. Several lines of evidence show that both bacteria and viruses are vulnerable to autophagic destruction and that successful pathogens have evolved strategies to avoid autophagy, or to actively subvert its components, to promote their own replication. The molecular mechanisms of the avoidance and subversion of autophagy by microorganisms will be the subject of much future research, not only to study their roles in the replication of these microorganisms, but also because they will provide — as bacteria and viruses so often have — unique tools to study the cellular process itself.
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