Loss of PPR protein Ppr2 induces ferroptosis-like cell death in Schizosaccharomyces pombe

Liu, Zecheng; Ebrahim, Alia; Wu, Xiaoyu; Li, Minjie; Huang, Ying

doi:10.1007/s00203-022-02970-2

Cited by 8 publications

(9 citation statements)

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“…The Δ sls1 cells began to lose viability after 36 h of incubation and lost most of their viability at 48 h of incubation (Figure 3b). This phenotype is also seen in other S. pombe respiratory deficient mutants (Z. Liu et al, 2022; Su et al, 2017). These results suggest that S. pombe Sls1 is required for mitochondrial respiration.…”

Section: Resultsmentioning

confidence: 53%

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Schizosaccharomyces pombe Sls1 is primarily required for cox1 mRNA translation

Wang

Luo

Huang

2022

Yeast

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Mitochondrial DNA (mtDNA) encodes essential subunits of the oxidative phosphorylation (OXPHOS) complexes; thus, the expression of mtDNA‐encoded genes is essential for the synthesis of adenosine triphosphate. However, factors involved in mitochondrial translation have not been fully characterized. In this study, we characterized Schizosaccharomyces pombe Sls1, which has sequence similarity to Saccharomyces cerevisiae Sls1 that is required for the translation of all mtDNA‐encoded messenger RNAs (mRNAs). Deletion of S. pombe sls1 severely impaired the growth of the cells on a rich medium containing the nonfermentable carbon source glycerol, which requires mitochondrial respiration. We found that the translation of mtDNA‐encoded Cox1, the largest subunit of the cytochrome c oxidase complex, was severely impaired in Δsls1 cells. Deletion of S. pombe sls1 also resulted in a barely detectable steady‐state level of mature cox1 mRNA. RNA immunoprecipitation showed that S. pombe Sls1 interacts with cox1 mRNA. Sucrose gradient sedimentation analysis revealed that S. pombe Sls1 is associated with the small subunit of mitochondrial ribosomes. Our results suggest that unlike S. cerevisiae Sls1, S. pombe Sls1 is primarily required for the accumulation and translation of cox1 mRNA.

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Section: Resultsmentioning

confidence: 53%

“…pombe respiratory deficient mutants (Z. Liu et al, 2022;Su et al, 2017). These results suggest that S. pombe Sls1 is required for mitochondrial respiration.…”

Section: Deletion Of S Pombe Sls1 Causes a Respiratory Growth Defect ...mentioning

confidence: 99%

Schizosaccharomyces pombe Sls1 is primarily required for cox1 mRNA translation

Wang

Luo

Huang

2022

Yeast

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“…By decreasing the Fe concentration, grx1 continued to exhibit the highest expression level, while spfep1 expression decreased and spPhp4 expression increased ( Figure 8 ). When iron levels are low, S. pombe cells inhibit the transcription of many genes that encode iron-utilizing proteins ( Labbé et al, 2007 ; Liu et al, 2022 ). Interacting with the CCAAT-binding complex composed of spPhp2, spPhp3, and spPhp5, spPhp4 modulates transcription ( Mercier et al, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

“…Low-intracellular iron concentration inhibits the activity of Fe-dependent enzymes, while high iron accumulation stimulates reactive oxygen species (ROS) formation and disrupts other metal-trafficking pathways ( Vachon et al, 2012 ; Chen et al, 2022 ). Therefore, cells must tightly regulate iron uptake to maintain an equilibrium between adequate and excessive concentrations ( Liu et al, 2022 ). In this regard, the fission yeast Schizosaccharomyces pombe (sp) uses two transcription factors, spFep1 and spPhp4, to regulate iron levels within cells ( Mercier et al, 2006 ; Jbel et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Schizosaccharomyces pombe Grx4, Fep1, and Php4: In silico analysis and expression response to different iron concentrations

et al. 2022

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Due to iron’s essential role in cellular metabolism, most organisms must maintain their homeostasis. In this regard, the fission yeast Schizosaccharomyces pombe (sp) uses two transcription factors to regulate intracellular iron levels: spFep1 under iron-rich conditions and spPhp4 under iron-deficient conditions, which are controlled by spGrx4. However, bioinformatics analysis to understand the role of the spGrx4/spFep1/spPhp4 axis in maintaining iron homeostasis in S. pombe is still lacking. Our study aimed to perform bioinformatics analysis on S. pombe proteins and their sequence homologs in Aspergillus flavus (af), Saccharomyces cerevisiae (sc), and Homo sapiens (hs) to understand the role of spGrx4, spFep1, and spPhp4 in maintaining iron homeostasis. The three genes’ expression patterns were also examined at various iron concentrations. A multiple sequence alignment analysis of spGrx4 and its sequence homologs revealed a conserved cysteine residue in each PF00085 domain. Blast results showed that hsGLRX3 is most similar to spGrx4. In addition, spFep1 is most closely related in sequence to scDal80, whereas scHap4 is most similar to spFep1. We also found two highly conserved motifs in spFep1 and its sequence homologs that are significant for iron transport systems because they contain residues involved in iron homeostasis. The scHap4 is most similar to spPhp4. Using STRING to analyze protein-protein interactions, we found that spGrx4 interacts strongly with spPhp4 and spFep1. Furthermore, spGrx4, spPhp4, and spFep1 interact with spPhp2, spPhp3, and spPhp5, indicating that the three proteins play cooperative roles in iron homeostasis. At the highest level of Fe, spgrx4 had the highest expression, followed by spfep1, while spphp4 had the lowest expression; a contrast occurred at the lowest level of Fe, where spgrx4 expression remained constant. Our findings support the notion that organisms develop diverse strategies to maintain iron homeostasis.

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“…Although most studies on ferroptosis have been performed in mammalian systems, an ancestral form of ferroptotic cell death has been observed in organisms ranging from cyanobacteria and plants to Saccharomyces pombe and trypanosomes (Bogacz and Krauth-Siegel, 2018;Aguilera et al, 2022;Liu et al, 2022). In Saccharomyces pombe, a ferroptosis-like form of cell death has been observed in response to deletion of a pentatricopeptide repeat (PPR) gene, ppr2, which encodes a general mitochondrial translation factor (Liu et al, 2022). In the African trypanosome, Trypanosoma brucei, mutations in tryparedoxin peroxidase, an ortholog of glutathione peroxidase 4, results in several ultrastructural changes in mitochondria that are reminiscent of ferroptosis.…”

Section: A Rudimentary Form Of Ferroptosis Has Been Observed In Multi...mentioning

confidence: 99%

Dissecting the mechanism of regulation of a ferroptosis-like form of cell death in Drosophila melanogaster

Saini

Owusu-Ansah

2023

Front. Cell Death

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Ferroptosis is a specific form of non-apoptotic cell death that is driven by iron-dependent phospholipid peroxidation. Research over the past decade has contributed to our understanding of how this important cell death process is regulated in mammalian systems, especially with regard to the distinct modes of induction, the role of metabolic signals, the organelles involved, implications of ferroptosis for development and aging, and how our improved understanding of the process can be exploited for therapeutic purposes. Other studies have described variants of this ancient cell death process in cyanobacteria, plants and protozoans. Emerging evidence indicates that a ferroptosis-like form of cell death exists in fruit flies (Drosophila melanogaster). Due to the extensive homology of genes in Drosophila melanogaster and Drosophila suzukii, unique aspects of ferroptosis in Drosophila melanogaster may be of particular relevance for developing targeted pesticides against Drosophila suzukii—a major invasive agricultural pest of the berry and wine industry in Southeast Asia, Europe and America. Further, aspects of ferroptosis in Drosophila melanogaster that are conserved in insects in general may provide the basis for identifying new insecticides for controlling the spread of vector-borne diseases such as malaria. In this perspective, we highlight some of the studies in Drosophila melanogaster that have sought to improve our understanding of the ferroptosis-like form of cell death that operates in this organism and conclude with a discussion of the opportunities and challenges for studying this phenomenon in fruit flies.

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Loss of PPR protein Ppr2 induces ferroptosis-like cell death in Schizosaccharomyces pombe

Cited by 8 publications

References 35 publications

Schizosaccharomyces pombe Sls1 is primarily required for cox1 mRNA translation

Schizosaccharomyces pombe Sls1 is primarily required for cox1 mRNA translation

Schizosaccharomyces pombe Grx4, Fep1, and Php4: In silico analysis and expression response to different iron concentrations

Dissecting the mechanism of regulation of a ferroptosis-like form of cell death in Drosophila melanogaster

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