Bach Institute of Biochemistry, Federal Research Centre of Biotechnology, Russian Academy of Sciences, Moscow, 119071, Russia.
Biochemistry (Mosc). 2019 Jan;84(Suppl 1):S225-S232. doi: 10.1134/S000629791914013X.
Mitochondria play a crucial role in energy production, general cell metabolism, cell signaling, and apoptosis. Mitochondria are also the main source of reactive oxygen species, especially in the case of their dysfunction. Therefore, damaged or even superfluous mitochondria not required for normal cell functioning represent risk factors and should be removed in order to maintain cell homeostasis. Mitochondria removal occurs via mitophagy, a type of selective autophagy (from Greek autos, self and phagein, to eat) that takes place in parallel with mitochondrial biogenesis and other processes. This review outlines general views on autophagy and mitophagy and summarizes information on the autophagy-related (Atg) proteins and their complexes involved in these processes. Yeast, especially Saccharomyces cerevisiae, is a convenient model system for studying molecular mechanisms of mitophagy because yeast genome, transcriptome, and proteome have been well characterized and because genetic manipulations with yeast are relatively simple and fast. Furthermore, yeast contain a number of orthologs of human proteins. Mitophagy in yeast is promoted by various factors, such as starvation, aging, oxidative stress, mitochondrial dysfunction, signaling proteins, and modification of mitochondrial proteins. In this review, we discuss molecular mechanisms underlying mitophagy and its regulation in yeast and present examples of relationships between mitophagy and ubiquitination-deubiquitination processes, as well as between mitophagy and other types of autophagy.
线粒体在能量产生、一般细胞代谢、细胞信号转导和细胞凋亡中起着至关重要的作用。线粒体也是活性氧物种的主要来源,尤其是在其功能障碍的情况下。因此,对于正常细胞功能不需要的受损甚至多余的线粒体代表着风险因素,应该被清除,以维持细胞内环境稳定。线粒体的清除通过自噬发生,自噬是一种选择性自噬(来自希腊语 autos,自我和 phagein,吃),与线粒体生物发生和其他过程平行发生。这篇综述概述了自噬和线粒体自噬的一般观点,并总结了与这些过程相关的自噬相关(Atg)蛋白及其复合物的信息。酵母,特别是酿酒酵母,是研究线粒体自噬分子机制的便利模型系统,因为酵母的基因组、转录组和蛋白质组已经得到了很好的描述,并且酵母的遗传操作相对简单和快速。此外,酵母中含有许多人类蛋白质的同源物。各种因素如饥饿、衰老、氧化应激、线粒体功能障碍、信号蛋白和线粒体蛋白的修饰都可以促进酵母中的线粒体自噬。在这篇综述中,我们讨论了酵母中线粒体自噬的分子机制及其调控,并举例说明了线粒体自噬与泛素化-去泛素化过程之间的关系,以及与其他类型自噬之间的关系。