Loss of epitranscriptomic control of selenocysteine utilization engages senescence and mitochondrial reprogramming^☆.

ABSTRACT: Critically important to the maintenance of the glutathione (GSH) redox cycle are the activities of many selenocysteine-containing GSH metabolizing enzymes whose translation is controlled by the epitranscriptomic writer alkylation repair homolog 8 (ALKBH8). ALKBH8 is a tRNA methyltransferase that methylates the wobble uridine of specific tRNAs to regulate the synthesis of selenoproteins. Here we demonstrate that a deficiency in the writer ALKBH8 (Alkbh8^def), alters selenoprotein levels and engages senescence, regulates stress response genes and promotes mitochondrial reprogramming. Alkbh8^def mouse embryonic fibroblasts (MEFs) increase many hallmarks of senescence, including senescence associated β-galactosidase, heterocromatic foci, the cyclin dependent kinase inhibito

SUBMITTER: Lee MY 

PROVIDER: S-EPMC6904832 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature