Chemical Genetics Screen of EVP4593 Sensitivity in Budding Yeast Identifies Effects on Mitochondrial Structure and Function
Year: 2023
Type: article
Abstract: , an ABC transporter that confers multidrug resistance. To better understand the cellular pathways and processes affected by EVP4593, we conducted a genome-wide chemical genetics screen of the yeast knockout collection. The objective was to identify yeast gene deletion strains that exhibit growth defects when subjected to a sublethal concentration of EVP4593 [15µM]. Our screen identified 21 yeast genes that are required for resistance to 15µM EVP4593 in glycerol-containing media. The genes identified in our screen are functionally involved in several distinct categories including mitochondrial structure and function, translational regulation and nutritional sensing, cellular stress response and detoxification. Additionally, we identified cellular phenotypes associated with the exposure to EVP4593, including changes in mitochondrial structure. In conclusion, our study represents the first genome-wide screen in yeast to identify the genetic pathways and cell-protective mechanisms involved in EVP4593 resistance and reveals that this small molecule inhibitor affects both mitochondrial structure and function.
Source: PubMed Central
Institutions: William & Mary, University of Hohenheim
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4376642829