Fluorescent fatty acid conjugates for live cell imaging of peroxisomes.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 May 2024
21 May 2024
Historique:
received:
25
04
2023
accepted:
09
05
2024
medline:
22
5
2024
pubmed:
22
5
2024
entrez:
21
5
2024
Statut:
epublish
Résumé
Peroxisomes are eukaryotic organelles that are essential for multiple metabolic pathways, including fatty acid oxidation, degradation of amino acids, and biosynthesis of ether lipids. Consequently, peroxisome dysfunction leads to pediatric-onset neurodegenerative conditions, including Peroxisome Biogenesis Disorders (PBD). Due to the dynamic, tissue-specific, and context-dependent nature of their biogenesis and function, live cell imaging of peroxisomes is essential for studying peroxisome regulation, as well as for the diagnosis of PBD-linked abnormalities. However, the peroxisomal imaging toolkit is lacking in many respects, with no reporters for substrate import, nor cell-permeable probes that could stain dysfunctional peroxisomes. Here we report that the BODIPY-C12 fluorescent fatty acid probe stains functional and dysfunctional peroxisomes in live mammalian cells. We then go on to improve BODIPY-C12, generating peroxisome-specific reagents, PeroxiSPY650 and PeroxiSPY555. These probes combine high peroxisome specificity, bright fluorescence in the red and far-red spectrum, and fast non-cytotoxic staining, making them ideal tools for live cell, whole organism, or tissue imaging of peroxisomes. Finally, we demonstrate that PeroxiSPY enables diagnosis of peroxisome abnormalities in the PBD CRISPR/Cas9 cell models and patient-derived cell lines.
Identifiants
pubmed: 38773129
doi: 10.1038/s41467-024-48679-2
pii: 10.1038/s41467-024-48679-2
doi:
Substances chimiques
4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4314Subventions
Organisme : Human Frontier Science Program (HFSP)
ID : LT000559/2021-L
Informations de copyright
© 2024. The Author(s).
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