Cardiac mitochondrial dynamics: miR-mediated regulation during cardiac injury

- Mitochondrial structural integrity is determined by dynamic and counter-balanced fusion and fission events.
- Altered expression of fusion/fission proteins are seen in deteriorating mitochondrial bioenergetics and metabolism during cardiac stress.
- MiRNAs regulate several molecular signalling mechanisms, including fusion/fission events.
- Dysregulation of the target-specific mRNA-miRNA interaction is associated with progression of cardiac pathogenesis.
- Nuclear genome-encoded microRNAs dictate mitochondrial genome translation, biogenesis, dynamics and apoptosis.
- MiRNAs of nuclear or mt. genome localized in mitochondria raises questions on their import/export mechanisms, stability and functions.
- Cardiomyocyte homeostasis, nuclear/mt-miRNA and mitochondrial dynamics: Elucidating this triangular link can offer drug targets for CVDs.

Mitochondrial integrity is indispensable for cardiac health. With the advent of modern imaging technologies, mitochondrial motility and dynamics within the cell are extensively studied. Terminally differentiated and well-structured cardiomyocytes depict little mitochondrial division and fusion, questioning the contribution of mitochondrial fusion proteins (Mitofusin 1/2 and Optic Atrophy 1 protein) and fission factors (Dynamin-like protein 1 and mitochondrial fission 1 protein) in cardiomyocyte homeostasis. Emerging evidences suggest that alterations in mitochondrial morphology from globular, elongated network to punctate fragmented disconnected structures are a pathological response to ensuing cardiac stress and cardiomyocyte cell death, bringing forth the following question, “what maintains this balance between fusion and fission?” The answer hinges upon the classical “junk” DNA: microRNAs, the endogenous non-coding RNAs. Because of their essential role in numerous signaling pathways, microRNAs are considered to play major roles in the pathogenesis of various diseases. Mitochondria are not exempted from microRNA-mediated regulation. This review defines the importance of mitochondrial structural integrity and the microRNA-mitochondrial dynamics tandem, an imminent dimension of the cardiac homeostasis network. Elucidating their coordinated interaction could spur RNA-based therapeutics for resuscitating functional mitochondrial population during cardiovascular disorders.