Mitochondrial ncRNAs: From Pathological Regulation to Targeted Therapy in Cardiovascular Diseases

Heart failure (HF) is closely linked to mitochondrial dysfunction, featured by abnormal energy metabolism, excessive reactive oxygen species (ROS), and imbalanced mitochondrial dynamics. Clinically, effective targeted therapies for mitochondrial dysfunction are still lacking, which aggravates HF and multi-organ injury. Mitochondrial non-coding RNAs (mt-ncRNAs) form a regulatory network critical for mitochondrial function. Among them, mitochondrial-encoded circular RNAs (mecciRNAs) and mitochondrial double-stranded RNAs (mt-dsRNAs) are research hotspots. mecciRNAs protect the heart by assisting protein import and regulating mitochondrial pores and ROS; their degradation worsens HF, while exogenous supplementation alleviates injury. mt-dsRNAs arise from aberrant mitochondrial transcription and contribute to myocardial injury and remodeling via MAVS, cGAS-STING, and PNPT1 pathways. Gene therapy targeting mecciRNAs and mt-dsRNAs combined with mitochondrial delivery represents a promising strategy for HF treatment.