Isotropic super-resolution light-sheet microscopy of dynamic intracellular structures at subsecond timescales

Yi, Zhao; Zhang, Meng; Zhang, Wenting; Zhou, Yao; Chen, Longbiao; Liu, Qing; Wang, Peng; Chen, Rong; Duan, Xinxin; Chen, Feifan; Deng, Huan; Wei, Yunfei; Fei, Peng; Zhang, Yuhui

doi:10.1038/s41592-022-01395-5

Cited by 73 publications

(54 citation statements)

References 48 publications

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“…Notably, we find evidence for l-Opa1 play important roles in maintaining CJ shape and connectivity, which correlates well with WT-like apoptotic responses for cells containing mainly l-Opa1. This work motivates further studies visualizing and dissecting mechanisms underlying cristae lifecycles by new live cell imaging approaches to gain insight into spatio-temporal regulation of cristae (Stephan et al, 2019;Kleele et al, 2021;Zhao et al, 2022). Future structural and live cell imaging studies will also be necessary to directly relate how specific protein conformational states influence such morphologies.…”

Section: Discussionmentioning

confidence: 92%

In situarchitecture of Opa1-dependent mitochondrial cristae remodeling

Fry

Navarro

Qin

et al. 2023

Preprint

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Cristae membrane state plays a central role in regulating mitochondrial function and cellular metabolism. The protein Optic atrophy 1 (Opa1) is an important crista remodeler that exists as two forms in the mitochondrion, a membrane-anchored long form (l-Opa1) and a processed short form (s-Opa1). The mechanisms for how Opa1 influences cristae shape have remained unclear due to the lack of native 3D views of cristae morphology. We perform in situ cryo-electron tomography of cryo-focused ion beam milled mouse embryonic fibroblasts to understand how each form of Opa1 influences cristae architecture. In our tomograms, we observe elongated mitochondria with a stacking phenotype, and an absence of tubular cristae, when only l-Opa1 is present. In contrast, when mitochondria contain mainly s-Opa1, we observe irregular cristae packing, an increase in globular cristae, and decreased matrix condensation. Notably, we find the absence of l-Opa1 results in mitochondria with wider cristae junctions. BH3 profiling reveals that absence of l-Opa1 reduces cytochrome c release in response to pro-apoptotic stimuli. We discuss the implications Opa1-dependent cristae morphologies in cell death initiation.

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Section: Discussionmentioning

confidence: 92%

In situarchitecture of Opa1-dependent mitochondrial cristae remodeling

Fry

Navarro

Qin

et al. 2023

Preprint

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“…[214][215][216] The application of DL to mitochondrial SRI is a good example of interdisciplinary achievements. 217,218 As DL and SRM technologies advance, it may be possible to combine DL with sophisticated microscopy technology to achieve intelligent augmented microscopy with SRI and highcontent, efficient, real-time, objective image analysis. 219,220 Furthermore, improving the image resolution has always been a major research topic in the computer field.…”

Section: Discussionmentioning

confidence: 99%

Small-molecule fluorogenic probes for mitochondrial nanoscale imaging

et al. 2023

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“…SRM techniques provide powerful tools for observing subcellular structures with a spatial resolution beyond the diffraction limit and have been widely used in the life sciences [31][32][33][34] . However, their applications in blood-based disease diagnosis are rare and preliminary.…”

Section: Discussionmentioning

confidence: 99%

“…Thanks to recently developed superresolution uorescence microscopy (SRM) techniques, subcellular structures have been visualized with a resolution down to tens of nanometers [31][32][33][34] . Compared to EM, SRM offers easier sample preparation, higher labeling speci city, and a signi cantly higher throughput.…”

Section: Introductionmentioning

confidence: 99%

Superresolution fluorescence microscopy of platelet subcellular structures as a potential tumor liquid biopsy

Zhang

Deng

et al. 2023

Preprint

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Blood-based tumor liquid biopsies are promising as an alternative or complement to tissue biopsies due to their noninvasiveness, convenience, and safety, and there is still a great demand for the discovery of new biomarkers for these biopsies. Here, we present nanoscale distribution patterns of subcellular structures in platelets, as imaged by structured illumination superresolution fluorescence microscopy, as a new type of potential biomarker for tumor liquid biopsies. We established a standardized protocol for platelet sample preparation and developed an automated high-throughput image analysis workflow. We explored the diagnostic capability based on the statistical analysis of 200,000 superresolution images of individual platelets from a variety of tumor patients, benign mass patients, and healthy volunteers (n=163). Our results suggest that the nanoscale distribution patterns of α-granules in platelets have the potential to be biomarkers for several cancers, including glioma and cervical, endometrial and ovarian cancers, facilitating not only diagnosis but also therapeutic monitoring. This study provides a promising novel type of platelet parameter for tumor liquid biopsies at the subcellular level rather than the existing cellular or molecular level and opens up a new avenue for clinical applications of superresolution imaging techniques.

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Isotropic super-resolution light-sheet microscopy of dynamic intracellular structures at subsecond timescales

Cited by 73 publications

References 48 publications

In situarchitecture of Opa1-dependent mitochondrial cristae remodeling

In situarchitecture of Opa1-dependent mitochondrial cristae remodeling

Small-molecule fluorogenic probes for mitochondrial nanoscale imaging

Superresolution fluorescence microscopy of platelet subcellular structures as a potential tumor liquid biopsy

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