title: Mitochondrial pathways to cardiac recovery: TFAM.
abstract: Mitochondrial dysfunction underlines a multitude of pathologies; however, studies are scarce that rescue the mitochondria for cellular resuscitation. Exploration into the protective role of mitochondrial transcription factor A (TFAM) and its mitochondrial functions respective to cardiomyocyte death are in need of further investigation. TFAM is a gene regulator that acts to mitigate calcium mishandling and ROS production by wrapping around mitochondrial DNA (mtDNA) complexes. TFAM's regulatory functions over serca2a, NFAT, and Lon protease contribute to cardiomyocyte stability. Calcium- and ROS-dependent proteases, calpains, and matrix metalloproteinases (MMPs) are abundantly found upregulated in the failing heart. TFAM's regulatory role over ROS production and calcium mishandling leads to further investigation into the cardioprotective role of exogenous TFAM. In an effort to restabilize physiological and contractile activity of cardiomyocytes in HF models, we propose that TFAM-packed exosomes (TFAM-PE) will act therapeutically by mitigating mitochondrial dysfunction. Notably, this is the first mention of exosomal delivery of transcription factors in the literature. Here we elucidate the role of TFAM in mitochondrial rescue and focus on its therapeutic potential.
authors.affiliation: Department of Physiology and Biophysics, Health Sciences Centre, 1216, School of Medicine, University of Louisville, 500, South Preston Street, Louisville, KY, 40202, USA.
authors.forename: George H
authors.initials: GH
authors.lastname: Kunkel
authors.affiliation: Department of Physiology and Biophysics, Health Sciences Centre, 1216, School of Medicine, University of Louisville, 500, South Preston Street, Louisville, KY, 40202, USA. p0chat03@louisville.edu.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Chaturvedi
authors.affiliation: Department of Physiology and Biophysics, Health Sciences Centre, 1216, School of Medicine, University of Louisville, 500, South Preston Street, Louisville, KY, 40202, USA.
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Tyagi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D055354:Exosomes / Q000378:metabolism; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C499631:TFAM protein, human; D014157:Transcription Factors; D002154:Calpain; D020782:Matrix Metalloproteinases; D002118:Calcium
keywords: Calpain; Hsp60; MMPs; Mitochondria; Serca2a; TFAM