Grabiński Wojciech, Kicińska Anna, Funtowicz Karolina, Skrzypczak Tomasz, Karachitos Andonis
Department of Bioenergetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland.
Center for Advanced Technology, Adam Mickiewicz University, Poznań, Poland.
Sci Rep. 2025 Jul 18;15(1):26106. doi: 10.1038/s41598-025-11993-w.
Saccharomyces cerevisiae has proven to be an invaluable model organism for studying mitochondrial function owing to its genetic tractability and the high conservation of mitochondrial processes among eukaryotes, including humans. Yeasts are easy to culture and manipulate genetically, which allows rapid generation of mutant strains and detailed dissection of mitochondrial pathways. In addition, the ability of yeasts to survive without functional mitochondria allows the study of mutations that are lethal to organisms that are dependent on aerobic metabolism. Taking advantage of these benefits, we investigated the toxicity of SARS-CoV-2 main protease (Mpro) expression in yeast under conditions that enforce mitochondria-dependent aerobic metabolism. Our results showed that Mpro expression was highly toxic and significantly impaired yeast growth. Pronounced changes in the morphology and mitochondrial function were observed, indicating that mitochondrial pathways are exceptionally sensitive to Mpro activity. These results provide insights that may be relevant for understanding the effects of Mpro in more complex eukaryotic systems.
由于其遗传易处理性以及线粒体过程在包括人类在内的真核生物中具有高度保守性，酿酒酵母已被证明是研究线粒体功能的一种极其重要的模式生物。酵母易于培养且能进行基因操作，这使得能够快速产生突变菌株并对线粒体途径进行详细剖析。此外，酵母在没有功能性线粒体的情况下仍能存活，这使得对依赖有氧代谢的生物体具有致死性的突变得以研究。利用这些优势，我们在强制线粒体依赖的有氧代谢条件下，研究了新型冠状病毒2型主要蛋白酶（Mpro）在酵母中的毒性。我们的结果表明，Mpro的表达具有高度毒性，并显著损害酵母生长。观察到线粒体形态和功能发生了明显变化，表明线粒体途径对Mpro活性异常敏感。这些结果为理解Mpro在更复杂的真核系统中的作用提供了相关见解。
