{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cotticelli MG"],"funding":["Children's Hospital of Philadelphia","Hamilton and Finneran Families","NIDDK NIH HHS","Children's Hospital of Philadelphia","NINDS NIH HHS","Friedreich's Ataxia Research Alliance","Friedreich's Ataxia Research Alliance"],"pagination":["dmm049497"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9637271"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(5)"],"pubmed_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 affected by frataxin knockdown. We confirmed that, in iPSC-derived cardiomyocytes, loss of frataxin leads to mitochondrial dysfunction. The type I interferon response was activated in multiple cell types following acute frataxin knockdown and was caused, at least in part, by release of mitochondrial DNA into the cytosol, activating the cGAS-STING sensor pathway."],"journal":["Disease models & mechanisms"],"pubmed_title":["Acute frataxin knockdown in induced pluripotent stem cell-derived cardiomyocytes activates a type I interferon response."],"pmcid":["PMC9637271"],"funding_grant_id":["P30 DK019525","R01 NS124640"],"pubmed_authors":["Rozo AV","Napierala JS","Yang W","Cotticelli MG","Wilson RB","Chen J","Doliba NM","Xia S","Truitt R","Tobias JW","Lee T","Napierala M"],"additional_accession":[]},"is_claimable":false,"name":"Acute frataxin knockdown in induced pluripotent stem cell-derived cardiomyocytes activates a type I interferon response.","description":"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 affected by frataxin knockdown. We confirmed that, in iPSC-derived cardiomyocytes, loss of frataxin leads to mitochondrial dysfunction. The type I interferon response was activated in multiple cell types following acute frataxin knockdown and was caused, at least in part, by release of mitochondrial DNA into the cytosol, activating the cGAS-STING sensor pathway.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 May","modification":"2026-05-27T23:42:40.576Z","creation":"2024-12-04T12:30:22.593Z"},"accession":"S-EPMC9637271","cross_references":{"pubmed":["36107856"],"doi":["10.1242/dmm.049497"]}}