title: Chromosome 21-derived hsa-miR-155-5p regulates mitochondrial biogenesis by targeting Mitochondrial Transcription Factor A (TFAM).
abstract: The regulation of mitochondrial biogenesis is under the control of nuclear genes including the master Mitochondrial Transcription Factor A (TFAM). Recent evidence suggests that the expression of TFAM is regulated by microRNAs (miRNAs) in various cellular contexts. Here, we show that hsa-miR-155-5p, a prominent miRNA encoded in chromosome 21, controls the expression of TFAM at the post-transcriptional level. In human fibroblasts derived from a diploid donor, downregulation of TFAM by hsa-miR-155-5p decreased mitochondrial DNA (mtDNA) content. In contrast, downregulation of TFAM by hsa-miR-155-5p did not decrease mtDNA content in fibroblasts derived from a donor with Down syndrome (DS, trisomy 21). In line, downregulation of mitochondrial TFAM levels through hsa-miR-155-5p decreased mitochondrial mass in diploid fibroblasts but not in trisomic cells. Due to the prevalence of mitochondrial dysfunction and cardiac abnormalities in subjects with DS, we examined the presence of potential associations between hsa-miR-155-5p and TFAM expression in heart samples from donors with and without DS. There were significant negative associations between hsa-miR-155-5p and TFAM expression in heart samples from donors with and without DS. These results suggest that regulation of TFAM by hsa-miR-155-5p impacts mitochondrial biogenesis in the diploid setting but not in the DS setting.
authors: Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, USA.
authors: Adolfo
authors: A
authors: Quiñones-Lombraña
authors: Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, USA. Electronic address: jgblanco@buffalo.edu.
authors: Javier G
authors: JG
authors: Blanco
mesh_terms: D000818:Animals; D016466:CHO Cells; D016022:Case-Control Studies; D002478:Cells, Cultured; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D004272:DNA, Mitochondrial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004314:Down Syndrome / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D063269:Mitochondrial Turnover; D032383:Myocytes, Cardiac / Q000378:metabolism; D011003:Ploidies; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D024101:Mitochondrial Proteins; C499631:TFAM protein, human; D014157:Transcription Factors
keywords: Down syndrome; Hsa-miR-155-5p; Mitochondrial biogenesis; TFAM