Biology subjects

Izgi, H.

Publications and source records attributed to Izgi, H..

3 recordsLinked to original sources

bioRxiv2025

Yippee-like protein Moh1 links gene expression to metabolism and selective stress resistance in Saccharomyces cerevisiae

The Yippee-like (YPEL) proteins are a conserved eukaryotic gene family implicated in proliferation, senescence, and stress adaptation. In humans, five paralogs (YPEL1-YPEL5) are widely expressed and encode proteins with high sequence and amino acid similarity, yet the molecular basis of their functions remains poorly defined. While conservation implies possible functional redundancy, the distinct roles of each YPEL paralog have not been defined. The budding yeast S. cerevisiae possesses a single ortholog, MOH1, which contributes to survival and stress responses and can be functionally complemented by human YPELs. However, the cellular role of MOH1 remains to be elucidated. Here, we investigated the function of MOH1 in S. cerevisiae. MOH1 deletion (moh1{Delta}) conferred sensitivity to sodium azide and sulfuric acid but increased resistance to hydrogen peroxide and acetic acid. Moh1 protein levels decreased upon hydrogen peroxide treatment and increased following sulfuric acid exposure, indicating stress-dependent regulation. Light and scanning electron microscopy showed that moh1{Delta} cells are constitutively rounder, tend to form clumps, and exhibit rough surface features, indicating altered cellular architecture. RNA profiling and FTIR spectroscopy revealed transcriptional reprogramming and metabolic remodeling in moh1{Delta} cells, including alterations in lipid, protein, and cell wall polysaccharide levels and composition. Intracellular ROS assays indicated that hydrogen peroxide resistance can be attributed to decreased cellular uptake resulting from altered permeability, rather than changes in mitochondrial ROS production. Collectively, our findings identify Moh1 as a regulatory factor linking gene expression to metabolism and cellular architecture, influencing membrane permeability and conferring selective stress resistance in S. cerevisiae.

cell biology↗

bioRxiv2022

Under the shadow: Old-biased genes are subject to weak purifying selection at both the tissue and cell type-specific levels

The mutation accumulation theory predicts that aging is caused by accumulation of late-acting deleterious variants in the germ-line, due to weak purifying selection at old age. In accordance with this model, we and others have shown that sequence conservation among old-biased genes (with higher expression in old versus young adults) is weaker than among young-biased genes across a number of mammalian and insect species. However, questions remained regarding the source and generality of this observation. It was especially unclear whether the observed patterns were driven by tissue and cell type composition shifts or by cell-autonomous expression changes during aging. How wide this trend would extend to non-mammalian metazoan aging was also uncertain. Here we analyzed bulk tissue as well as cell type-specific RNA sequencing data from diverse animal taxa across six different datasets from five species. We show that the previously reported age-related decrease in transcriptome conservation (ADICT) is commonly found in aging tissues of non-mammalian species, including non-mammalian vertebrates (chicken brain, killifish liver and skin) and invertebrates (fruit fly brain). Analyzing cell type-specific transcriptomes of adult mice, we further detect the same ADICT trend at the single cell type level. Old-biased genes are less conserved across the majority of cell types analyzed in the lung, brain, liver, muscle, kidney, and skin, and these include both tissue-specific cell types, and also ubiquitous immune cell types. Overall, our results support the notion that aging in metazoan tissues may be at least partly shaped by the mutation accumulation process.

evolutionary biology↗

bioRxiv2021

Inter-tissue convergence of gene expression and loss of cellular identity during ageing

Developmental trajectories of gene expression may reverse in their direction during ageing, a phenomenon previously linked to cellular identity loss. Our analysis of cerebral cortex, lung, liver and muscle transcriptomes of 16 mice, covering development and ageing intervals, revealed widespread but tissue-specific ageing-associated expression reversals. Cumulatively, these reversals create a unique phenomenon: mammalian tissue transcriptomes diverge from each other during postnatal development, but during ageing, they tend to converge towards similar expression levels, a process we term Divergence followed by Convergence, or DiCo. We found that DiCo was most prevalent among tissue-specific genes and associated with loss of tissue identity, which is confirmed using data from independent mouse and human datasets. Further, using publicly available single-cell transcriptome data, we showed that DiCo could be driven both by alterations in tissue cell type composition and also by cell-autonomous expression changes within particular cell types.

genomics↗