This study, co-authored by researchers from both Bio2Q and Keio University, demonstrates how newly synthesized proteins can be visualized and tracked in living cells using long-wavelength fluorescent probes, enabling real-time observation of protein degradation dynamics.

Maintaining protein homeostasis through the balanced synthesis and degradation of proteins is essential for cellular health, yet existing methods for monitoring newly synthesized proteins typically require cell fixation, or they lack compatibility with live-cell imaging, limiting their ability to capture these dynamic processes. Here, this team of researchers developed two fluorescent probes that selectively label newly synthesized proteins in living cells, allowing their fate to be followed over time without disrupting cellular function. The approach was used to revealed the gradual degradation of newly synthesized proteins through both proteasomal and lysosomal pathways and further showed that protein turnover is impaired in drug-induced senescent cells, where newly synthesized proteins accumulate because of reduced lysosomal activity.

By enabling continuous visualization of protein synthesis and degradation in living cells, this study establishes a versatile platform for investigating proteostasis and provides a valuable tool for studying the molecular mechanisms underlying aging, neurodegenerative disorders, cancer, and other diseases associated with disrupted protein homeostasis.