Acute frataxin knockdown in induced pluripotent stem cell-derived cardiomyocytes activates a type I interferon response.

ABSTRACT: Friedreich ataxia, the most common hereditary ataxia, is a neuro- and cardio-degenerative disorder caused, in most cases, by decreased expression of the mitochondrial protein frataxin. Cardiomyopathy is the leading cause of premature death. Frataxin functions in the biogenesis of iron-sulfur clusters, which are prosthetic groups that are found in proteins involved in many biological processes. To study the changes associated with decreased frataxin in human cardiomyocytes, we developed a novel isogenic model by acutely knocking down frataxin, post-differentiation, in cardiomyocytes derived from induced pluripotent stem cells (iPSCs). Transcriptome analysis of four biological replicates identified severe mitochondrial dysfunction and a type I interferon response as the pathways most affecte

SUBMITTER: Cotticelli MG 

PROVIDER: S-EPMC9637271 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature