Mitochondria–lysosome contact sites (MLCs) are essential for cellular homeostasis, including metabolic regulation and organelle quality control. Since these interactions occur at nanometer-scale distances, their organization cannot be fully resolved using conventional fluorescence microscopy. In this application note, we investigate the nanoscale interplay between TOM20-labelled mitochondria and LAMP-positive lysosomal structures using SMLM on the Abbelight SAFe MN360 platform. By combining spectral demixing with Abbelight’s patented ASTER illumination technology, simultaneous imaging of up to three colors can be achieved while accelerating acquisition and enabling homogeneous large-field illumination for high-throughput STORM and DNA-PAINT imaging. This approach provides a powerful framework for studying organelle crosstalk with high localization precision across large cellular populations.
