Spatiotemporally Tracking the Programmable Mitochondrial Membrane Potential Evolutions by a Robust Molecular Rotor

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Probes

Background:

• Mitochondrial membrane potential (MMP) is crucial for cellular function, but its accurate detection is challenging due to limitations of conventional probes.
• Existing probes suffer from photobleaching, inconvenience, and irreversibility, hindering precise MMP monitoring.

Purpose of the Study:

• To introduce a novel, spatial-dependent fluorescent molecular rotor, Mito-Cy, for efficient tracking of MMP variations.
• To demonstrate Mito-Cy's utility in monitoring MMP status through its distinct localization in cellular compartments.

Main Methods:

• Development and characterization of Mito-Cy, a fluorescent molecular rotor sensitive to intramolecular rotation.
• Systematic investigation of Mito-Cy's distribution within mitochondria and nucleus under varying MMP conditions.
• Assessment of Mito-Cy's photostability, sensitivity, and applicability in monitoring reversible MMP changes.

Main Results:

• Mito-Cy concentrates in mitochondria under normal MMP, indicating healthy cellular state.
• Mito-Cy migrates from mitochondria to the nucleus as MMP decreases, providing a visual indicator of declining potential.
• Mito-Cy exclusively accumulates in the nucleus when MMP vanishes, signifying cell death or severe dysfunction.
• Mito-Cy exhibits high photostability and sensitivity, enabling programmable monitoring of MMP evolution and logic-gate operations.

Conclusions:

• Mito-Cy is a robust and versatile fluorescent probe for real-time, spatial-dependent monitoring of MMP in living cells.
• Its unique localization behavior allows for precise assessment of MMP status and dynamics.
• Mito-Cy holds significant potential for illuminating mitochondrial viscosity-related bioprocesses and cellular health diagnostics.