A DNA nanomachine chemically resolves lysosomes in live cells

Area of Science:

• Cell Biology
• Biochemistry
• Genetics

Background:

• Lysosomes are vital organelles involved in cellular processes like autophagy and degradation.
• Lysosomal dysfunction is linked to neurodegenerative and storage diseases, but mechanisms remain unclear.
• Existing live imaging methods show distinct lysosome subpopulations, but chemical characterization is limited.

Purpose of the Study:

• To develop a chemical method for resolving lysosome subpopulations in live cells.
• To apply this method to study lysosomal heterogeneity and its relevance in disease.

Main Methods:

• Developed a DNA-based reporter for simultaneous imaging of lysosome pH and chloride.
• Named the technology two-ion measurement (2-IM).
• Applied 2-IM to primary skin fibroblasts from healthy individuals and Niemann-Pick disease patients.

Main Results:

• Identified two distinct lysosome populations in healthy fibroblasts using 2-IM.
• Observed the absence of one specific lysosome population in Niemann-Pick disease patient cells.
• Demonstrated the re-emergence of this population upon therapeutic treatment of patient cells.

Conclusions:

• 2-IM enables precise chemical resolution of lysosome subpopulations in live cells.
• This technology can help elucidate the role of specific lysosome populations in disease.
• 2-IM offers a potential tool for monitoring disease progression and evaluating therapeutic efficacy in lysosomal disorders.