Novel Nile Blue Analogue Stains Yeast Vacuolar Membrane, Endoplasmic Reticulum and Lipid Droplets, Inducing Cell Death through Vacuole Membrane Permeabilization
| Autor: | João C. C. Ferreira, Carla D. Lopes, Ana Preto, Maria João Sousa, Maria S. T. Gonçalves |
|---|---|
| Přispěvatelé: | Universidade do Minho |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Programmed cell death QH301-705.5 Plant Science Vacuole 01 natural sciences vacuole/lysosome membrane permeabilization Article 03 medical and health sciences chemistry.chemical_compound Lipid droplet Biology (General) Ecology Evolution Behavior and Systematics 030304 developmental biology benzo[a]phenoxazine derivative 0303 health sciences Ciências Naturais::Ciências Biológicas Science & Technology vacuole lysosome membrane permeabilization 010405 organic chemistry Endoplasmic reticulum cell death mechanism yeast as a eukaryotic cell model Nile blue 3. Good health 0104 chemical sciences Cell biology Cytosol chemistry Nile Blue analogue Phenoxazine Intracellular |
| Zdroj: | Journal of Fungi Volume 7 Issue 11 Journal of Fungi, Vol 7, Iss 971, p 971 (2021) |
| ISSN: | 2309-608X |
| DOI: | 10.3390/jof7110971 |
| Popis: | Phenoxazine derivatives such as Nile Blue analogues are assumed to be increasingly relevant in cell biology due to their fluorescence staining capabilities and antifungal and anticancer activities. However, the mechanisms underlying their effects remain poorly elucidated. Using S. cerevisiae as a eukaryotic model, we found that BaP1, a novel 5- and 9-N-substituted benzo[a]phenoxazine synthesized in our laboratory, when used in low concentrations, accumulates and stains the vacuolar membrane and the endoplasmic reticulum. In contrast, at higher concentrations, BaP1 stains lipid droplets and induces a regulated cell death process mediated by vacuolar membrane permeabilization. BaP1 also induced mitochondrial fragmentation and depolarization but did not lead to ROS accumulation, changes in intracellular Ca2+, or loss of plasma membrane integrity. Additionally, our results show that the cell death process is dependent on the vacuolar protease Pep4p and that the vacuole permeabilization results in its translocation from the vacuole to the cytosol. In addition, although nucleic acids are commonly described as targets of benzo[a]phenoxazines, we did not find any alterations at the DNA level. Our observations highlight BaP1 as a promising molecule for pharmacological application, using vacuole membrane permeabilization as a targeted approach. Joao C. C. Ferreira (SFRH/BD/133207/2017) acknowledges a doctoral grant (from the Fundacao para a Ciencia e Tecnologia) FCT. This work was supported by the strategic programs UIDB/04050/2020, UID/QUI/0686/2016 and UID/QUI/0686/2019 funded by national funds through the FCT I.P. Thanks are due to FCT for financial support to the Portuguese NMR network (PTNMR), Bruker Avance III 400-Univ. Minho. This work was also funded by FCT within the scope of the project PTDC/QUIQIN/28662/2017. |
| Databáze: | OpenAIRE |
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