Imaging phenotype reveals that disulfirams induce protein insolubility in the mitochondrial matrix.

ABSTRACT: The cell painting assay is useful for understanding cellular phenotypic changes and drug effects. To identify other aspects of well-known chemicals, we screened 258 compounds with the cell painting assay and focused on a mitochondrial punctate phenotype seen with disulfiram. To elucidate the reason for this punctate phenotype, we looked for clues by examining staining steps and gene knockdown as well as examining protein solubility and comparing cell lines. From these results, we found that the punctate phenotype was caused by protein insolubility in the mitochondrial matrix. Interestingly, the punctate phenotype of disulfiram was sensitive to the relative expression of LonP1, a protease in the mitochondrial matrix that regulates proteostasis, suggesting that the punctate phenotype manifes

SUBMITTER: Ohno K 

PROVIDER: S-EPMC11682119 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature