Jiangsu Key Laboratory for Microbes and Functional Genetics, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China; School of Public Health, Hubei University of Medicine, Shiyan 442000, China.
Jiangsu Key Laboratory for Microbes and Functional Genetics, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Mitochondrion. 2024 May;76:101875. doi: 10.1016/j.mito.2024.101875. Epub 2024 Mar 16.
Pentatricopeptide repeat proteins are involved in mitochondrial both transcriptional and posttranscriptional regulation. Schizosaccharomyces pombe Ppr2 is a general mitochondrial translation factor that plays a critical role in the synthesis of all mitochondrial DNA-encoded oxidative phosphorylation subunits, which are essential for mitochondrial respiration. Our previous analysis showed that ppr2 deletion resulted in increased expression of iron uptake genes and caused ferroptosis-like cell death in S. pombe. In the present work, we showed that deletion of ppr2 reduced viability on glycerol- and galactose-containing media.Php4 is a transcription repressor that regulates iron homeostasis in fission yeast. We found that in the ppr2 deletion strain, Php4 was constitutively active and accumulated in the nucleus in the stationary phase. We also found that deletion of ppr2 decreased the ferroptosis-related protein Gpx1 in the mitochondria. Overexpression of Gpx1 improves the viability of Δppr2 cells. We showed that the deletion of ppr2 increased the production of ROS, downregulated heme synthesis and iron-sulfur cluster proteins, and induced stress proteins. Finally, we observed the nuclear accumulation of Pap1-GFP and Sty1-GFP, suggesting that Sty1 and Pap1 in response to cellular stress in the ppr2 deletion strain. These results suggest thatppr2 deletion may cause mitochondrial dysfunction, which is likely to lead to iron-sensing defect and iron starvation response, resulting in perturbation of iron homeostasis and increased hydroxyl radical production. The increased hydroxyl radical production triggers cellular responses in theppr2 deletion strain.
五肽重复蛋白参与线粒体的转录和转录后调控。裂殖酵母 Ppr2 是一种通用的线粒体翻译因子，在所有线粒体 DNA 编码的氧化磷酸化亚基的合成中发挥着关键作用，这些亚基对于线粒体呼吸是必不可少的。我们之前的分析表明，ppr2 缺失导致铁摄取基因的表达增加，并导致裂殖酵母中的铁死亡样细胞死亡。在本工作中，我们表明 ppr2 的缺失降低了在含有甘油和半乳糖的培养基上的生存能力。Php4 是一种转录抑制剂，调节裂殖酵母中的铁稳态。我们发现，在 ppr2 缺失菌株中，Php4 持续激活并在静止期积累在核内。我们还发现，ppr2 的缺失减少了线粒体中的铁死亡相关蛋白 Gpx1。Gpx1 的过表达提高了 Δppr2 细胞的生存能力。我们表明，ppr2 的缺失增加了 ROS 的产生，下调了血红素合成和铁硫簇蛋白，并诱导了应激蛋白。最后，我们观察到 Pap1-GFP 和 Sty1-GFP 的核积累，表明 Sty1 和 Pap1 对 ppr2 缺失菌株中的细胞应激作出反应。这些结果表明，ppr2 的缺失可能导致线粒体功能障碍，这可能导致铁感应缺陷和铁饥饿反应，从而导致铁稳态失调和羟基自由基产生增加。增加的羟基自由基产生触发了 ppr2 缺失菌株中的细胞反应。
