Cells respond to salt stress by osmolyte synthesis and by increase of K⁺ uptake and Na⁺ efflux at the plasma membrane and of Na⁺ accumulation at the vacuole. This cellular level of response has been approached by the molecular genetics of Saccharomyces cerevisiae. Two plasma membrane proteins, Sln1 and Sho1, operate as sensors for turgor loss under mild osmotic stress. They activate the Hog1 MAP kinase which induces several defence genes, including the ENA1 Na⁺-efflux pump. Hog1-mediated induction occurs by inactivation of the Sko1 repressor. High concentrations of Na⁺ activate the calcium-dependent protein phosphatase calcineurin, which induces the ENA1 gene via the positive transcription factor Hal8/Crz1/Tcn1. Vacuoles could operate as Na⁺ sensors through a Na⁺-Ca²⁺ exchange mechanism. The electrical potential of the plasma membrane is a major determinant of the uptake of toxic cations, including Na⁺, by non-specific leakage pathways. This biophysical parameter is modulated by the concerted activities of the proton pumping Pma1 ATPase and the Trk1,2 K⁺ uptake system. Both calcineurin and the protein kinase Hal4,5 modulate Trk1,2 and, indirectly, the membrane potential and salt tolerance. The limiting role of vacuolar cation accumulation in salt tolerance has been demonstrated by expression in yeast vacuoles of the bacterial antiporter NhaA.

Exposure of yeast to increases in extracellular osmolarity activates the Hog1 mitogen‐activated protein kinase (MAPK), which is essential for the induction of gene expression required for cell survival upon osmotic stress. Several genes are regulated in response to osmotic stress by Sko1, a transcriptional repressor of the ATF/CREB family. We show by in vivo coprecipitation and phosphorylation studies that Sko1 and Hog1 interact and that Sko1 is phosphorylated upon osmotic stress in a Hog1‐dependent manner. Hog1 phosphorylates Sko1 in vitro at multiple sites within the N‐terminal region. Phosphorylation of Sko1 disrupts the Sko1–Ssn6–Tup1 repressor complex, and consistently, a mutant allele of Sko1, unphosphorylatable by Hog1, exhibits less derepression than the wild type. Interestingly, Sko1 repressor activity is further enhanced in strains with high protein kinase A (PKA) activity. PKA phosphorylates Sko1 near the bZIP domain and mutation of these sites eliminates modulation of Sko1 responses to high PKA activity. Thus, Sko1 transcriptional repression is controlled directly by the Hog1 MAPK in response to stress, and this effect is further modulated by an independent signaling mechanism through the PKA pathway.

Aging is considered the deterioration of physiological functions along with an increased mortality rate. This scientific review focuses on the central importance of genomic instability during the aging process, encompassing a range of cellular and molecular changes that occur with advancing age. In particular, this revision addresses the genetic and epigenetic alterations that contribute to genomic instability, such as telomere shortening, DNA damage accumulation, and decreased DNA repair capacity. Furthermore, the review explores the epigenetic changes that occur with aging, including modifications to histones, DNA methylation patterns, and the role of non-coding RNAs. Finally, the review discusses the organization of chromatin and its contribution to genomic instability, including heterochromatin loss, chromatin remodeling, and changes in nucleosome and histone abundance. In conclusion, this review highlights the fundamental role that genomic instability plays in the aging process and underscores the need for continued research into these complex biological mechanisms.

Antifungal resistance is a growing concern as it poses a significant threat to public health. Fungal infections are a significant cause of morbidity and mortality, especially in immunocompromised individuals. The limited number of antifungal agents and the emergence of resistance have led to a critical need to understand the mechanisms of antifungal drug resistance. This review provides an overview of the importance of antifungal resistance, the classes of antifungal agents, and their mode of action. It highlights the molecular mechanisms of antifungal drug resistance, including alterations in drug modification, activation, and availability. In addition, the review discusses the response to drugs via the regulation of multidrug efflux systems and antifungal drug–target interactions. We emphasize the importance of understanding the molecular mechanisms of antifungal drug resistance to develop effective strategies to combat the emergence of resistance and highlight the need for continued research to identify new targets for antifungal drug development and explore alternative therapeutic options to overcome resistance. Overall, an understanding of antifungal drug resistance and its mechanisms will be indispensable for the field of antifungal drug development and clinical management of fungal infections.

Hyperosmotic stress triggers a great variety of adaptive responses in eukaryotic cells that affect many different physiological functions. Here we investigate the role of the mitochondria during osmostress adaptation in budding yeast. Mitochondrial function is generally required for proper salt and osmotic stress adaptation because mutants with defects in many different mitochondrial components show hypersensitivity to increased NaCl and KCl concentrations. Mitochondrial protein abundance rapidly increases upon osmoshock in a selective manner, because it affects Calvin cycle enzymes (Sdh2 and Cit1) and components of the electron transport chain (Cox6) but not the ATP synthase complex (Atp5). Transcription of the SDH2, CIT1, and COX6 genes is severalfold induced within the first minutes of osmotic shock, dependent to various degree on the Hog1 and Snf1 protein kinases. Mitochondrial succinate dehydrogenase enzyme activity is stimulated upon osmostress in a Snf1-dependent manner. The osmosensitivity of mitochondrial mutants is not caused by impaired stress-activated transcription or by a general depletion of the cellular ATP pool during osmostress. We finally show that the growth defect of mitochondrial mutants in high salt medium can be partially rescued by supplementation of glutathione. Additionally, mitochondrial defects cause the hyperaccumulation of reactive oxygen species during salt stress. Our results indicate that the antioxidant function of the mitochondria might play an important role in adaptation to hyperosmotic stress.