MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes

Metabolic syndrome increases the risk for cardiovascular disease including metabolic cardiomyopathy that may progress to heart failure. The decline in mitochondrial metabolism is considered a critical pathogenic mechanism that drives this progression. Considering its cardiac specificity, we hypothes...

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Autores principales:	Naveen Mekala, Jacob Kurdys, Alexis Paige Vicenzi, Leana Rose Weiler, Carmen Avramut, Edwin J. Vazquez, Neli Ragina, Mariana G. Rosca
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cardiomyocytes metabolic syndrome miR 208a mitochondrial biogenesis bioenergetics Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f1f92ff0eb804f2db78f178c44600698
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spelling	oai:doaj.org-article:f1f92ff0eb804f2db78f178c446006982021-11-25T17:12:00ZMiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes10.3390/cells101131522073-4409https://doaj.org/article/f1f92ff0eb804f2db78f178c446006982021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3152https://doaj.org/toc/2073-4409Metabolic syndrome increases the risk for cardiovascular disease including metabolic cardiomyopathy that may progress to heart failure. The decline in mitochondrial metabolism is considered a critical pathogenic mechanism that drives this progression. Considering its cardiac specificity, we hypothesized that miR 208a regulates the bioenergetic metabolism in human cardiomyocytes exposed to metabolic challenges. We screened in silico for potential miR 208a targets focusing on mitochondrial outcomes, and we found that mRNA species for mediator complex subunit 7, mitochondrial ribosomal protein 28, stanniocalcin 1, and Sortin nexin 10 are rescued by the CRISPR deletion of miR 208a in human SV40 cardiomyocytes exposed to metabolic challenges (high glucose and high albumin-bound palmitate). These mRNAs translate into proteins that are involved in nuclear transcription, mitochondrial translation, mitochondrial integrity, and protein trafficking. MiR 208a suppression prevented the decrease in myosin heavy chain α isoform induced by the metabolic stress suggesting protection against a decrease in cardiac contractility. MiR 208a deficiency opposed the decrease in the mitochondrial biogenesis signaling pathway, mtDNA, mitochondrial markers, and respiratory properties induced by metabolic challenges. The benefit of miR 208a suppression on mitochondrial function was canceled by the reinsertion of miR 208a. In summary, miR 208a regulates mitochondrial biogenesis and function in cardiomyocytes exposed to diabetic conditions. MiR 208a may be a therapeutic target to promote mitochondrial biogenesis in chronic diseases associated with mitochondrial defects.Naveen MekalaJacob KurdysAlexis Paige VicenziLeana Rose WeilerCarmen AvramutEdwin J. VazquezNeli RaginaMariana G. RoscaMDPI AGarticlecardiomyocytesmetabolic syndromemiR 208amitochondrial biogenesisbioenergeticsBiology (General)QH301-705.5ENCells, Vol 10, Iss 3152, p 3152 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cardiomyocytes metabolic syndrome miR 208a mitochondrial biogenesis bioenergetics Biology (General) QH301-705.5
spellingShingle	cardiomyocytes metabolic syndrome miR 208a mitochondrial biogenesis bioenergetics Biology (General) QH301-705.5 Naveen Mekala Jacob Kurdys Alexis Paige Vicenzi Leana Rose Weiler Carmen Avramut Edwin J. Vazquez Neli Ragina Mariana G. Rosca MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes
description	Metabolic syndrome increases the risk for cardiovascular disease including metabolic cardiomyopathy that may progress to heart failure. The decline in mitochondrial metabolism is considered a critical pathogenic mechanism that drives this progression. Considering its cardiac specificity, we hypothesized that miR 208a regulates the bioenergetic metabolism in human cardiomyocytes exposed to metabolic challenges. We screened in silico for potential miR 208a targets focusing on mitochondrial outcomes, and we found that mRNA species for mediator complex subunit 7, mitochondrial ribosomal protein 28, stanniocalcin 1, and Sortin nexin 10 are rescued by the CRISPR deletion of miR 208a in human SV40 cardiomyocytes exposed to metabolic challenges (high glucose and high albumin-bound palmitate). These mRNAs translate into proteins that are involved in nuclear transcription, mitochondrial translation, mitochondrial integrity, and protein trafficking. MiR 208a suppression prevented the decrease in myosin heavy chain α isoform induced by the metabolic stress suggesting protection against a decrease in cardiac contractility. MiR 208a deficiency opposed the decrease in the mitochondrial biogenesis signaling pathway, mtDNA, mitochondrial markers, and respiratory properties induced by metabolic challenges. The benefit of miR 208a suppression on mitochondrial function was canceled by the reinsertion of miR 208a. In summary, miR 208a regulates mitochondrial biogenesis and function in cardiomyocytes exposed to diabetic conditions. MiR 208a may be a therapeutic target to promote mitochondrial biogenesis in chronic diseases associated with mitochondrial defects.
format	article
author	Naveen Mekala Jacob Kurdys Alexis Paige Vicenzi Leana Rose Weiler Carmen Avramut Edwin J. Vazquez Neli Ragina Mariana G. Rosca
author_facet	Naveen Mekala Jacob Kurdys Alexis Paige Vicenzi Leana Rose Weiler Carmen Avramut Edwin J. Vazquez Neli Ragina Mariana G. Rosca
author_sort	Naveen Mekala
title	MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes
title_short	MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes
title_full	MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes
title_fullStr	MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes
title_full_unstemmed	MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes
title_sort	mir 208a regulates mitochondrial biogenesis in metabolically challenged cardiomyocytes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f1f92ff0eb804f2db78f178c44600698
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MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes

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