Scheckhuber Christian Q, Hamann Andrea, Brust Diana, Osiewacz Heinz D
Faculty of Biosciences, Institute of Molecular Biosciences and Cluster of Excellence Macromolecular Complexes, Johann Wolfgang Goethe University, 60438, Frankfurt/Main, Germany,
Subcell Biochem. 2012;57:233-50. doi: 10.1007/978-94-007-2561-4_11.
Cellular quality control pathways are needed for maintaining the biological function of organisms. If these pathways become compromised, the results are usually highly detrimental. Functional impairments of cell components can lead to diseases and in extreme cases to organismal death. Dysfunction of cells can be induced by a number of toxic by-products that are formed during metabolic activity, like reactive oxygen and nitrogen species, for example. A key source of reactive oxygen species (ROS) are the organelles of oxidative phosphorylation, mitochondria. Therefore mitochondrial function is also directly affected by ROS, especially if there is a compromised ROS-scavenging capacity. Biological systems therefore depend on several lines of defence to counteract the toxic effects of ROS and other damaging agents. The first level is active at the molecular level and consists of various proteases that bind and degrade abnormally modified and / or aggregated mitochondrial proteins. The second level is concerned with maintaining the quality of whole mitochondria. Among the pathways of this level are mitochondrial dynamics and autophagy (mitophagy). Mitochondrial dynamics describes the time-dependent fusion and fission of mitochondria. It is argued that this kind of organellar dynamics has the power to restore the function of impaired organelles by content mixing with intact organelles. If the first and second lines of defence against damage fail and mitochondria become damaged too severely, there is the option to remove affected cells before they can elicit more damage to their surrounding environment by apoptosis. This form of programmed cell death is strictly regulated by a complex network of interacting components and can be divided into mitochondria-dependent and mitochondria-independent modes of action. In this review we give an overview on various biological quality control systems in fungi (yeasts and filamentous fungi) with an emphasis on autophagy (mitophagy) and apoptosis and how these pathways allow fungal organisms to maintain a balanced cellular homeostasis.
细胞质量控制途径对于维持生物体的生物学功能至关重要。如果这些途径受损，结果通常是极其有害的。细胞成分的功能障碍会导致疾病，在极端情况下会导致生物体死亡。细胞功能障碍可由代谢活动过程中形成的许多有毒副产物诱导产生，例如活性氧和氮物种。活性氧（ROS）的一个关键来源是氧化磷酸化的细胞器——线粒体。因此，线粒体功能也直接受到ROS的影响，尤其是在ROS清除能力受损的情况下。生物系统因此依赖于多条防御线来抵消ROS和其他损伤因子的毒性作用。第一级防御在分子水平上起作用，由各种蛋白酶组成，这些蛋白酶结合并降解异常修饰和/或聚集的线粒体蛋白。第二级防御涉及维持整个线粒体的质量。这一级别的途径包括线粒体动力学和自噬（线粒体自噬）。线粒体动力学描述了线粒体随时间的融合和分裂。有人认为，这种细胞器动力学能够通过与完整细胞器的内容物混合来恢复受损细胞器的功能。如果针对损伤的第一道和第二道防线失效，线粒体受损过于严重，那么可以在受影响的细胞对周围环境造成更多损伤之前通过凋亡将其清除。这种程序性细胞死亡形式受到一个由相互作用成分组成的复杂网络的严格调控，可分为依赖线粒体和不依赖线粒体的作用模式。在这篇综述中，我们概述了真菌（酵母和丝状真菌）中的各种生物质量控制系统，重点是自噬（线粒体自噬）和凋亡，以及这些途径如何使真菌生物体维持平衡的细胞内稳态。
