Mir 208a regulates mitochondrial biogenesis in metabolically challenged cardiomyocytes

Naveen Mekala, Jacob Kurdys, Alexis Paige Vicenze, Leana Rose Weiler, Carmen Avramut, Edwin J. Vazquez, Neli Ragina, Mariana G. Rosca

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Article number3152
JournalCells
Volume10
Issue number11
DOIs
StatePublished - Nov 2021

Keywords

  • Bioenergetics
  • Cardiomyocytes
  • Metabolic syndrome
  • MiR 208a
  • Mitochondrial biogenesis

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