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Reference - PMID:27886462 - Loss of ppr3, ppr4, ppr6, or ppr10 perturbs iron homeostasis and leads to apoptotic cell death in Schizosaccharomyces pombe.

Reference summary

PubMed ID
PMID:27886462
Title
Loss of ppr3, ppr4, ppr6, or ppr10 perturbs iron homeostasis and leads to apoptotic cell death in Schizosaccharomyces pombe.
Authors
Su Y, Yang Y, Huang Y
Citation
FEBS J 2017 Jan;284(2):324-337
Publication year
2017
Abstract
Pentatricopeptide repeat (PPR) proteins characterized by tandem arrays of a degenerate 35-amino-acid repeat belong to a large family of RNA-binding proteins that are involved in post-transcriptional control of organelle gene expression. PPR proteins are ubiquitous in eukaryotes, and particularly prevalent in higher plants. Schizosaccharomyces pombe has 10 PPR proteins. Among them, ppr3, ppr4, ppr6, and ppr10 participate in mitochondrial post-transcriptional processes and are required for mitochondrial electron transport chain (ETC) function. In the present work, we showed that deletion of ppr3, ppr4, ppr6, or ppr10 led to apoptotic cell death, as revealed by DAPI and Annexin V-FITC staining. These mutants also exhibited elevated levels of reactive oxygen species (ROS). RNA sequencing (RNA-seq) and quantitative RT-PCR analyses revealed that deletion of ppr10 affected critical biological processes. In particular, a core set of genes involved in iron uptake and/or iron homeostasis was elevated in the Δppr10 mutant, suggesting an elevated level of intracellular iron in the mutant. Consistent with this notion, Δppr3, Δppr4, Δppr6, and Δppr10 mutants exhibited increased sensitivity to iron. Furthermore, the iron chelator, bathophenanthroline disulfonic acid, but not the calcium chelator EGTA, nearly restored the viabilities of Δppr3, Δppr4, Δppr6, and Δppr10 mutants, and reduced ROS levels in the mutants. These results show for the first time that deletion of a ppr gene leads to perturbation of iron homeostasis. Our results also suggest that disrupted iron homeostasis in Δppr3, Δppr4, Δppr6, and Δppr10 mutants may lead to an increase in the level of ROS and induction of apoptotic cell death in S. pombe. The RNA-seq data have been deposited in the National Center for Biotechnology Information (NCBI) BioProject database (accession number SRP091623) and Gene Expression Omnibus (GEO) database (accession number GSE90144).

Annotation

Protein features

PBO:0111828 - PPR repeats

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Single locus phenotype

FYPO:0003730 - abolished cell population growth on galactose carbon source

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FYPO:0005826 - decreased level of generation of precursor metabolites and energy gene mRNA during vegetative growth

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FYPO:0001117 - decreased RNA level during vegetative growth

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FYPO:0001919 - fragmented nucleus during vegetative growth

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FYPO:0005760 - increased cell-cell adhesion

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FYPO:0002006 - increased cellular iron level

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FYPO:0003004 - increased cellular reactive oxygen species level during vegetative growth

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FYPO:0000377 - increased frequency of apoptosis

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FYPO:0005505 - increased level of cell surface glycoprotein gene mRNA during vegetative growth

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FYPO:0005420 - increased level of iron assimilation gene mRNA during vegetative growth

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FYPO:0002664 - increased level of stress responsive gene mRNA during vegetative growth

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FYPO:0005823 - increased phosphatidylserine externalization

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FYPO:0005824 - increased plasma membrane permeability

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FYPO:0000825 - increased RNA level during vegetative growth

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FYPO:0000245 - loss of viability in stationary phase

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FYPO:0001357 - normal vegetative cell population growth

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FYPO:0005825 - sensitive to iron

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FYPO:0003810 - small fragmented mitochondria present in increased numbers

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