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Updated: Jan 23, 2026
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Fabrication of Electrochemical-DNA Biosensors for the Reagentless Detection of Nucleic Acids, Proteins and Small Molecules
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DNA nanodevices detect an acidic nanolayer on the lysosomal surface
Yutong Zhang1,2,3, Meiqin Hu2,4, Yaping Meng2
1Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, China.
Nature Cell Biology
|January 21, 2026
Summary
Lysosomes create a unique acidic nanolayer on their exterior, regulated by TMEM175 (transmembrane protein 175). This surrounding acidity, not internal pH, controls lysosome positioning via cytosolic sensors.
Area of Science:
- Cell Biology
- Organelle Biology
- Biophysics
Background:
- Lysosomes require an acidic lumen for hydrolase activity.
- Mechanisms of proton leakage and regulation of cytosolic interactions are unclear.
Purpose of the Study:
- Investigate proton dynamics at the lysosomal surface.
- Identify factors regulating lysosomal positioning through pH sensing.
Main Methods:
- Development of DNA nanodevices for juxta-organellar pH monitoring.
- Cellular imaging and manipulation of TMEM175 activity.
Main Results:
- Discovery of a 21 nm thick acidic nanolayer (0.2-0.7 pH units lower than cytosol) on lysosomal exteriors.
- TMEM175 identified as the primary H+ efflux channel maintaining this nanolayer.
- Juxta-lysosomal acidity, not luminal acidity, regulates lysosome positioning via RILP sensing.
Conclusions:
- Lysosomes actively create an acidic extracellular nano-environment.
- This acidic nanolayer serves as a critical interface for cytosolic regulation of lysosome function and positioning.
- TMEM175 and juxta-lysosomal pH are key regulators of lysosome-cytosol interactions.
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