Peptide-Conjugated Probe Inducing Mitochondrial Dysfunction and Self-Reporting Cell Apoptosis by Aggregated Proteins

Area of Science:

• Biomedical Engineering
• Molecular Biology
• Cancer Research

Background:

• Real-time monitoring of cell apoptosis is vital for evaluating drug efficacy and preventing overtreatment.
• Current methods assessing cell membrane integrity fail to detect chronic cellular dysfunction due to proteostasis imbalance.
• Protein aggregation serves as a key indicator of cell apoptosis, offering a new avenue for detection.

Purpose of the Study:

• To develop a peptide-conjugated probe (QRKN) for inducing and self-reporting cell apoptosis via imaging of aggregated proteins.
• To investigate the mechanism by which QRKN induces mitochondrial dysfunction and subsequent apoptosis.
• To establish a sensitive method for monitoring therapeutic responses in real-time.

Main Methods:

• Design of a peptide-conjugated probe (QRKN) cleaved by cathepsin B (CB) into QRK and N components.
• QRK component induces mitochondrial membrane damage, cytochrome c (Cyt c) efflux, and caspase 3 expression.
• N component inhibits mitochondrial complex IV (Mito-IV) and reduces adenosine triphosphate (ATP) levels, leading to protein aggregation.

Main Results:

• QRKN effectively induces mitochondrial dysfunction through dual signaling pathways, culminating in protein aggregation and cell apoptosis.
• The probe exhibits high sensitivity to viscosity changes triggered by protein aggregation, enabling real-time apoptosis monitoring.
• QRKN successfully self-reports cell apoptosis, demonstrating its potential for monitoring therapeutic responses.

Conclusions:

• QRKN serves as a self-reporting probe for real-time monitoring of cell apoptosis by imaging protein aggregation.
• The probe induces mitochondrial dysfunction via cathepsin B-mediated cleavage, impacting key apoptotic pathways.
• QRKN provides valuable diagnostic information and facilitates the monitoring of therapeutic efficacy in cancer treatment.