Cell: New Super-resolution Imaging Technology Developed to Reveal New Phenomena of Organelle Interaction

Li Dong, Ph.D., of the Institute of Biophysics, Chinese Academy of Sciences, and Eric Betzig and Jennifer Lippincott-Schwartz, Ph.D., of the Howard Hughes Medical Research Institute of the United States, published a research paper in Cell entitled “Visualizing intracellular organelle and cytoskeletal interactions at nanoscale resolution on millisecond”. This paper pioneered the grazing incidence structured light illumination super-resolution imaging technology (GI-SIM), which can perform high-speed, long-term, super-resolution imaging of intracellular physiological processes. Using this technique, a variety of new interactions between organelles were discovered.


GI-SIM continuously images nearly 10,000 super-resolution images of living cells at 97 nm resolution and 266 frames per second. Compared with Li Dong’s previously developed total internal reflection structured light illumination super-resolution imaging technology (TIRF-SIM; Li et al., Science, 2015), the imaging depth of GI-SIM and the amount of signal generated are increased by 10 times. Compared to traditional confocal or turntable confocal microscopes, GI-SIM offers 2x higher spatial resolution and 10x faster imaging speeds; compared to other super-resolution imaging techniques, GI-SIM offers 10 times faster imaging speeds and 10-100 times longer imaging time spans over the cell size field of view. GI-SIM enables optimal two-dimensional super-resolution imaging of multiple organelle dynamics within the cell, which allows researchers to discover a variety of organelle interactions. For example:



(1) Three new extensions of tubular endoplasmic reticulum


The formation of the network structure of the endoplasmic reticulum is accomplished by the continuous extension and fusion of the tubular endoplasmic reticulum. Previous research work pointed out that there are two types of tubular endoplasmic reticulum extension: sliding and microtubule polymerization (pTAC). The study found three tubular endoplasmic reticulum extensions including microtubule depolymerization end traction (dTAC), hitchhiking, and microtubule-independent (Budding).


(2) The interaction between mitochondria and endoplasmic reticulum affects the division and fusion of mitochondria


Mitochondrial division is closely related to the endoplasmic reticulum. It is found that about 85% of mitochondrial division events occur at the contact sites of the mitochondria and the endoplasmic reticulum. The study further found that about 60% of mitochondrial fusion events occur at the mitochondrial and endoplasmic reticulum contact sites, and mitochondrial fusion events in contact with the endoplasmic reticulum are generally faster than those that do not interact with the endoplasmic reticulum.


(3) Multicolor GI-SIM imaging found that lysosomal-endoplasmic reticulum interaction plays a key role in regulating the dynamic transport and distribution of lysosomes in cells


(4) Past studies have only found that the endoplasmic reticulum can change its network structure through fusion. This study first observed that the lysosome in motion can cause transient rupture of the tubular endoplasmic reticulum.


(5) This study demonstrates for the first time in mammalian cells that there is extensive hitchhiking interaction between different species of organelles, and that morphological changes and migration of mitochondria, endoplasmic reticulum, and other organelles can be achieved by piggybacking onto other moving organelles without the need to recruit motor proteins directly.




Guo Y, Li D, Zhang S. et al. Visualizing Intracellular Organelle and Cytoskeletal Interactions at Nanoscale Resolution on Millisecond Timescales. Cell. 2018 Nov 15;175(5):1430-1442.e17. doi: 10.1016/j.cell.2018.09.057.

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