ArticleMolecular biology of the cell2008
Isc1p plays a key role in hydrogen peroxide resistance and chronological lifespan through modulation of iron levels and apoptosis.
Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 101 citations in OpenAlex.
- Predictive models of the genetic bases underlying budding yeast fitness in multiple environments.NAR genomics and bioinformatics · 2026Article
- Emerging evidence for a multitude of mechanisms and factors that determine amphotericin B resistance in pathogenic fungi.Cell surface (Amsterdam, Netherlands) · 2026Review
- Sphingolipid and methionine metabolism in aging.Journal of cell science · 2025Review
- Predictive models of the genetic bases underlying budding yeast fitness in multiple environments.bioRxiv : the preprint server for biology · 2025Article
- Dysregulation of ceramide metabolism causes phytoceramide-dependent induction of the unfolded protein response.Molecular biology of the cell · 2024Article
- Mitophagy in yeast: known unknowns and unknown unknowns.The Biochemical journal · 2023Review
- Effects of iron homeostasis on epigenetic age acceleration: a two-sample Mendelian randomization study.Clinical epigenetics · 2023Article
- The APC/C Activator Cdh1p Plays a Role in Mitochondrial Metabolic Remodelling in Yeast.International journal of molecular sciences · 2023Article
- Aft1 Nuclear Localization and Transcriptional Response to Iron Starvation Rely upon TORC2/Ypk1 Signaling and Sphingolipid Biosynthesis.International journal of molecular sciences · 2023Article
- Iron Metabolism in Aging and Age-Related Diseases.International journal of molecular sciences · 2022Review
- A Systematic Survey of Characteristic Features of Yeast Cell Death Triggered by External Factors.Journal of fungi (Basel, Switzerland) · 2021Review
- Yeast Sphingolipid Phospholipase GeneMolecular and cellular biology · 2020Article
- Pkh1p-Ypk1p and Pkh1p-Sch9p Pathways Are Activated by Acetic Acid to Induce a Mitochondrial-Dependent Regulated Cell Death.Oxidative medicine and cellular longevity · 2020Article
- Iron-dependent cleavage of ribosomal RNA during oxidative stress in the yeastThe Journal of biological chemistry · 2018Article
- Acetic acid induces Sch9p-dependent translocation of Isc1p from the endoplasmic reticulum into mitochondria.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2018Article
- The ceramide activated protein phosphatase Sit4 impairs sphingolipid dynamics, mitochondrial function and lifespan in a yeast model of Niemann-Pick type C1.Biochimica et biophysica acta. Molecular basis of disease · 2018Article
- Yeast Cells Exposed to Exogenous Palmitoleic Acid Either Adapt to Stress and Survive or Commit to Regulated Liponecrosis and Die.Oxidative medicine and cellular longevity · 2018Review
- A novel de novo dominant mutation inJournal of medical genetics · 2017Article
- Heterologous expression of anti-apoptotic human 14-3-3β/α enhances iron-mediated programmed cell death in yeast.PloS one · 2017Article
- The ceramide-activated protein phosphatase Sit4p controls lifespan, mitochondrial function and cell cycle progression by regulating hexokinase 2 phosphorylation.Cell cycle (Georgetown, Tex.) · 2016Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inositolphosphosphingolipid phospholipase C (Isc1p) of Saccharomyces cerevisiae belongs to the family of neutral sphingomyelinases that generates the bioactive sphingolipid ceramide. In this work the role of Isc1p in oxidative stress resistance and chronological lifespan was investigated. Loss of Isc1p resulted in a higher sensitivity to hydrogen peroxide that was associated with an increase in oxidative stress markers, namely intracellular oxidation, protein carbonylation, and lipid peroxidation. Microarray analysis showed that Isc1p deficiency up-regulated the iron regulon leading to increased levels of iron, which is known to catalyze the production of the highly reactive hydroxyl radicals via the Fenton reaction. In agreement, iron chelation suppressed hydrogen peroxide sensitivity of isc1Delta mutants. Cells lacking Isc1p also displayed a shortened chronological lifespan associated with oxidative stress markers and aging of parental cells was correlated with a decrease in Isc1p activity. The analysis of DNA fragmentation and caspase-like activity showed that Isc1p deficiency increased apoptotic cell death associated with oxidative stress and aging. Furthermore, deletion of Yca1p metacaspase suppressed the oxidative stress sensitivity and premature aging phenotypes of isc1Delta mutants. These results indicate that Isc1p plays an important role in the regulation of cellular redox homeostasis, through modulation of iron levels, and of apoptosis.
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