Recent Developments in Mitochondrial G‐Quadruplex Recognising Fluorescent Probes: A Review

Mitochondria is the cell's energy powerhouse and regulate most of the metabolism process through the inherent mitochondrial genes (mtDNA). The control of mtDNA replication and transcription is known to be mediated by noncanonical forms of guanine-rich nucleotides G-quadruplexes (G4s). These putative and transient guanine-based structures and their dynamics are closely associated with mtDNA deletion breakpoints pertaining to fatal diseases such as cancers, hypertension, diabetes, etc. The precise reason for the origin of G4s at deletion breakpoints in the heavy strand and during the replication process has not yet been identified, owing to its complex biochemical phenomenon. Biomolecular structure, typically having a size of 5–10 nm with an average life span of seconds, strongly demands high-end instruments to explore the precise biochemical mechanism and dynamics (folding or unfolding) in biological systems. In that sense, since the last decade, tremendous efforts have been kept in X-ray crystallography, circular dichroism spectroscopy (CD), nuclear magnetic resonance spectroscopy (NMR), immunofluorescence, and the mtG4-ChIP methods to recognize and characterize the G4s structures in physiological conditions. Owing to their non-invasiveness, robustness, and high spatio-temporal resolution at the molecular level, fluorescence methods have been exploited to recognize noncanonical forms of nucleic acids even at the subcellular level. In light of this, from 2015 until today, the documentation of photophysical and bioanalytical capabilities of mtG4s recognizing small and quencher-free fluorescent probes has not yet been reported. Considering the plethora of G4s propensity with mtDNA replication, transcription, oxidative phosphorylation, glycolysis etc. In the current article, we have systematically documented small fluorescent probes that have been exclusively used to recognize mtG4 in cellular conditions with photophysical and biophysical properties. Furthermore, the probe's designing rationale binding mechanism, readout system, cellular localization, and cytotoxicity were tabulated.