Heterochromatin epimutations impose mitochondrial dysfunction to confer antifungal resistance

ABSTRACT: Antifungal resistance in pathogenic fungi endanger global health and food supply. Wild-type fission yeast, Schizosaccharomyces pombe, can gain resistance to insults including caffeine and antifungal compounds through reversible epimutations. Resistant epimutants exhibit ectopic histone-H3K9 methylation-dependent heterochromatin islands, repressing underlying genes. Two genes whose heterochromatin island-induced repression causes resistance encode mitochondrial proteins: LYR-domain protein Cup1 and Cox1 translation regulator Ppr4. Genetic mutations, cup1-tt and ppr4, that phenocopy epimutants, cause mitochondrial dysfunction, including respiratory deficiency, poor growth on non-glucose carbon sources, and elevated reactive oxygen species. Transcriptomic analyses indicate cup1-tt and ppr4

SUBMITTER: Andreas Fellas 

PROVIDER: S-SCDT-10_1038-S44318-025-00649-0 | biostudies-other |

REPOSITORIES: biostudies-other