Language
English
Publication Date
7-1-2025
Journal
Nature Communications
DOI
10.1038/s41467-025-60546-2
PMID
40595486
PMCID
PMC12214859
PubMedCentral® Posted Date
7-1-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Mitochondrial membrane dynamics control the shape, number, and distribution of mitochondria and regulate energy production and cell health. In a screen for yeast mutants with increased levels of templated insertions (~10-1000 bp) in the nuclear genome, we identified mitochondrial fusion deficient mutants (mgm1Δ, ugo1Δ, fzo1Δ). We found that fusion mutants activate the iron regulon, have decreased iron-sulfur clusters (ISCs), and increased DNA damage, suggesting a role of iron homeostasis in preventing insertions. Consistently, a secondary screen found mutants affecting iron-sulfur cluster production (yfh1Δ, grx5Δ), vacuolar iron storage (ccc1Δ) or general iron homeostasis (aft1Δ) to exhibit high insertion levels. Treatment with iron chelators or hydrogen peroxide also increased insertions. We propose that iron dysregulation leading to oxidative DNA damage and compromised DNA repair drives insertions. These studies suggest that severe iron imbalance, associated with many human diseases and pharmacological treatments, can trigger genome instability in the form of templated insertions.
Keywords
Iron, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, DNA Damage, Mitochondrial Dynamics, Mitochondria, DNA Repair, Homeostasis, Mutation, Mutagenesis, Insertional, Hydrogen Peroxide, Genomic Instability, Iron-Sulfur Proteins, Transcription Factors, Genomic instability, Mitochondria, Chromosomes
Published Open-Access
yes
Recommended Citation
Fox, Jordan; Yu, Yang; Yu, Yang; et al., "Deficits in Mitochondrial Dynamics and Iron Balance Result in Templated Insertions" (2025). Faculty and Staff Publications. 5035.
https://digitalcommons.library.tmc.edu/baylor_docs/5035
Included in
Genetic Phenomena Commons, Genetic Processes Commons, Genetic Structures Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons