MicroRNA-regulated mitochondrial dysfunction in heart failure

Abstract

Heart failure (HF) is characterized by profound mitochondrial dysfunction, a central pathogenic mechanism driven by interconnected defects in metabolic dysregulation, excessive oxidative stress, impaired biogenesis, imbalanced dynamics, and defective mitophagy. This compromised mitochondrial fitness leads to bioenergetic deficiency, cardiomyocyte death, and progressive cardiac remodeling. MicroRNAs (miRNAs) have emerged as critical post-transcriptional regulators of mitochondrial homeostasis, capable of simultaneously modulating multiple components within these pathways. By fine-tuning the expression of key genes involved in fission/fusion, mitophagy, and biogenesis, miRNAs can either exacerbate or ameliorate HF progression, forming a complex and context-dependent regulatory network, and highlighting the potential of targeting the miRNA-mitochondria axis. However, clinical translation faces significant hurdles including target specificity, tissue-selective delivery and patient heterogeneity. Future research should focus on deciphering the mechanistic interplay between miRNA regulation and mitochondrial function in diverse HF contexts. This review aims to elucidate the molecular mechanisms by which miRNAs regulate mitochondrial dysfunction in HF, revealing novel therapeutic targets. A deeper understanding of this regulatory network is crucial for advancing HF management from symptom palliation toward mechanism-based precision medicine.

Keywords

MicroRNAs / heart failure / mitochondrial dysfunction / pathophysiology

References

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