ArticleGeroScience2020
Loss of vacuolar acidity results in iron-sulfur cluster defects and divergent homeostatic responses during aging in Saccharomyces cerevisiae.
Article in GeroScience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Vacuole pH loss triggers ESCRT-dependent plasma membrane remodeling to prevent amino acid toxicity.bioRxiv : the preprint server for biology · 2026Article
- Article
- Role of iron in brain development, aging, and neurodegenerative diseases.Annals of medicine · 2025Review
- Overexpression of Ssd1 and calorie restriction extend yeast replicative lifespan by preventing deleterious age-dependent iron uptake.bioRxiv : the preprint server for biology · 2025Article
- Transcriptome Analysis and CFEM Gene Overexpression inPathogens (Basel, Switzerland) · 2025Article
- Deficits in mitochondrial dynamics and iron balance result in templated insertions.Nature communications · 2025Article
- V-ATPase Disassembly at the Yeast Lysosome-Like Vacuole Is a Phenotypic Driver of Lysosome Dysfunction in Replicative Aging.Aging cell · 2025Article
- V-ATPase Disassembly at the Yeast Lysosome-Like Vacuole Is a Phenotypic Driver of Lysosome Dysfunction in Replicative Aging.bioRxiv : the preprint server for biology · 2024Article
- Iron Homeostatic Regulation in Saccharomyces cerevisiae: Introduction to a Computational Modeling Method.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Dietary change without caloric restriction maintains a youthful profile in ageing yeast.PLoS biology · 2023Article
- Long-term iron supplementation combined with vitamin B6 enhances maximal oxygen uptake and promotes skeletal muscle-specific mitochondrial biogenesis in rats.Frontiers in nutrition · 2023Article
- The Multifaceted Gene 275 Embedded in the PKS-PTS Gene Cluster Was Involved in the Regulation of Arthrobotrisin Biosynthesis, TCA Cycle, and Septa Formation in Nematode-Trapping FungusJournal of fungi (Basel, Switzerland) · 2022Article
- Article
- Deficiency of the RNA-binding protein Cth2 extends yeast replicative lifespan by alleviating its repressive effects on mitochondrial function.Cell reports · 2022Article
- Iron Metabolism in Aging and Age-Related Diseases.International journal of molecular sciences · 2022Review
- Article
- Article
- Mitochondrial-derived compartments facilitate cellular adaptation to amino acid stress.Molecular cell · 2021Article
- An energetics perspective on geroscience: mitochondrial protonmotive force and aging.GeroScience · 2021Article
- Cell-to-cell variation in gene expression and the aging process.GeroScience · 2021Review
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Authors and funding
29 authors.
Funding
Abstract
The loss of vacuolar/lysosomal acidity is an early event during aging that has been linked to mitochondrial dysfunction. However, it is unclear how loss of vacuolar acidity results in age-related dysfunction. Through unbiased genetic screens, we determined that increased iron uptake can suppress the mitochondrial respiratory deficiency phenotype of yeast vma mutants, which have lost vacuolar acidity due to genetic disruption of the vacuolar ATPase proton pump. Yeast vma mutants exhibited nuclear localization of Aft1, which turns on the iron regulon in response to iron-sulfur cluster (ISC) deficiency. This led us to find that loss of vacuolar acidity with age in wild-type yeast causes ISC defects and a DNA damage response. Using microfluidics to investigate aging at the single-cell level, we observe grossly divergent trajectories of iron homeostasis within an isogenic and environmentally homogeneous population. One subpopulation of cells fails to mount the expected compensatory iron regulon gene expression program, and suffers progressively severe ISC deficiency with little to no activation of the iron regulon. In contrast, other cells show robust iron regulon activity with limited ISC deficiency, which allows extended passage and survival through a period of genomic instability during aging. These divergent trajectories suggest that iron regulation and ISC homeostasis represent a possible target for aging interventions.
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