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Published in: Heart Failure Reviews 5/2016

01-09-2016

Mitochondrial pathways to cardiac recovery: TFAM

Authors: George H. Kunkel, Pankaj Chaturvedi, Suresh C. Tyagi

Published in: Heart Failure Reviews | Issue 5/2016

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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.
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Metadata
Title
Mitochondrial pathways to cardiac recovery: TFAM
Authors
George H. Kunkel
Pankaj Chaturvedi
Suresh C. Tyagi
Publication date
01-09-2016
Publisher
Springer US
Published in
Heart Failure Reviews / Issue 5/2016
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI
https://doi.org/10.1007/s10741-016-9561-8

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