Super-resolution imaging reveals the sub-diffraction phenotype of Zellweger Syndrome ghosts and wild-type peroxisomes

Scientific Reports
Kareem SolimanJ Gärtner

Abstract

Peroxisomes are ubiquitous cell organelles involved in many metabolic and signaling functions. Their assembly requires peroxins, encoded by PEX genes. Mutations in PEX genes are the cause of Zellweger Syndrome spectrum (ZSS), a heterogeneous group of peroxisomal biogenesis disorders (PBD). The size and morphological features of peroxisomes are below the diffraction limit of light, which makes them attractive for super-resolution imaging. We applied Stimulated Emission Depletion (STED) microscopy to study the morphology of human peroxisomes and peroxisomal protein localization in human controls and ZSS patients. We defined the peroxisome morphology in healthy skin fibroblasts and the sub-diffraction phenotype of residual peroxisomal structures ('ghosts') in ZSS patients that revealed a relation between mutation severity and clinical phenotype. Further, we investigated the 70 kDa peroxisomal membrane protein (PMP70) abundance in relationship to the ZSS sub-diffraction phenotype. This work improves the morphological definition of peroxisomes. It expands current knowledge about peroxisome biogenesis and ZSS pathoethiology to the sub-diffraction phenotype including key peroxins and the characteristics of ghost peroxisomes.

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Citations

Sep 17, 2018·Histochemistry and Cell Biology·Markus IslingerMichael Schrader
Aug 4, 2019·International Journal of Molecular Sciences·Anne Schieferdecker, Petra Wendler
Apr 1, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Josiah B PassmoreMichael Schrader
Aug 7, 2021·Biomolecules·Mirco SchilffSven Thoms
Mar 14, 2021·Microscopy Research and Technique·Zhaoyang WuPeng Xi

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Methods Mentioned

BETA
super-resolution microscopy
light microscopy
fluorescence microscopy
transfection
electron microscopy
biopsy
biopsies
immunoprecipitation
pull down
Co-immunoprecipitation

Software Mentioned

STED
ImageQuant
Image Studio
OriginPro
CellProflier
IsoData
Excel
ImageJ
Zeiss Axiovision
CellProfiler

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