Spatiotemporally Traceable Peptide Self-Assemblies for Mitochondrial-Specific Dysfunction.

Area of Science:

• Biotechnology
• Cell Biology
• Molecular Imaging

Background:

• Peptide self-assembly is a key strategy for creating functional agents that influence cellular fate.
• Challenges persist in achieving precise organelle localization and functional disruption via peptide self-assembly within complex intracellular environments.

Purpose of the Study:

• To develop a fluorescent peptide probe for spatiotemporally traceable organelle localization and functional perturbation.
• To visualize and report mitochondrial dysfunction using a self-assembling peptide system.

Main Methods:

• Development of T-FFVLK, a fluorescent peptide probe combining a mitochondria-targeting molecule with a self-assembling peptide.
• Tracking the probe's cellular entry, compartment localization, and self-assembly dynamics.
• Assessing probe-induced mitochondrial morphological and functional changes, including microtubule damage and cell cycle arrest.

Main Results:

• T-FFVLK successfully targets mitochondria, forming disruptive self-assembled structures and reporting mitochondrial dysfunction.
• The probe facilitates lysosomal escape and exhibits increased fluorescence upon mitochondrial localization.
• Mitochondrial enrichment occurred within 6 hours, with functional changes observed within 12 hours, leading to cell cycle arrest.

Conclusions:

• T-FFVLK serves as a valuable tool for observing mitochondrial dysfunction in real-time within living cells.
• The probe demonstrates significant potential for subcellular imaging applications.
• This self-assembling peptide system offers promise for future disease treatment strategies targeting mitochondria.