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Calcineurin-mediated intracellular organelle calcium homeostasis is required for the survival of fungal pathogens upon extracellular calcium stimuli
In eukaryotes, calcium not only is an essential mineral nutrient but also serves as an intracellular second messenger that is necessary for many physiological processes. Previous studies showed that the protein phosphatase-calcineurin protects fungi from toxicity caused by the extracellular calcium;...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043181/ https://www.ncbi.nlm.nih.gov/pubmed/33843471 http://dx.doi.org/10.1080/21505594.2021.1909954 |
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author | Zhang, Chi Ren, Yiran Gu, Huiyu Gao, Lu Zhang, Yuanwei Lu, Ling |
author_facet | Zhang, Chi Ren, Yiran Gu, Huiyu Gao, Lu Zhang, Yuanwei Lu, Ling |
author_sort | Zhang, Chi |
collection | PubMed |
description | In eukaryotes, calcium not only is an essential mineral nutrient but also serves as an intracellular second messenger that is necessary for many physiological processes. Previous studies showed that the protein phosphatase-calcineurin protects fungi from toxicity caused by the extracellular calcium; however, little is known about how calcineurin mediates the cellular physiology process for this function. In this study, by monitoring intracellular calcium, particularly by tracking vacuolar calcium dynamics in living cells through a novel procedure using modified aequorin, we found that calcineurin dysfunction systematically caused abnormal intracellular calcium homeostasis in cytosol, mitochondria, and vacuole, leading to drastic autophagy, global organelle fragmentation accompanied with the increased expression of cell death-related enzymes, and cell death upon extracellular calcium stimuli. Notably, all detectable defective phenotypes seen with calcineurin mutants can be significantly suppressed by alleviating a cytosolic calcium overload or increasing vacuolar calcium storage capacity, suggesting toxicity of exogenous calcium to calcineurin mutants is tightly associated with abnormal cytosolic calcium accumulation and vacuolar calcium storage capacity deficiency. Our findings provide insights into how the original recognized antifungal drug target-calcineurin regulates intracellular calcium homeostasis for cell survival and may have important implications for antifungal therapy and clinical drug administration. |
format | Online Article Text |
id | pubmed-8043181 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-80431812021-04-21 Calcineurin-mediated intracellular organelle calcium homeostasis is required for the survival of fungal pathogens upon extracellular calcium stimuli Zhang, Chi Ren, Yiran Gu, Huiyu Gao, Lu Zhang, Yuanwei Lu, Ling Virulence Research Paper In eukaryotes, calcium not only is an essential mineral nutrient but also serves as an intracellular second messenger that is necessary for many physiological processes. Previous studies showed that the protein phosphatase-calcineurin protects fungi from toxicity caused by the extracellular calcium; however, little is known about how calcineurin mediates the cellular physiology process for this function. In this study, by monitoring intracellular calcium, particularly by tracking vacuolar calcium dynamics in living cells through a novel procedure using modified aequorin, we found that calcineurin dysfunction systematically caused abnormal intracellular calcium homeostasis in cytosol, mitochondria, and vacuole, leading to drastic autophagy, global organelle fragmentation accompanied with the increased expression of cell death-related enzymes, and cell death upon extracellular calcium stimuli. Notably, all detectable defective phenotypes seen with calcineurin mutants can be significantly suppressed by alleviating a cytosolic calcium overload or increasing vacuolar calcium storage capacity, suggesting toxicity of exogenous calcium to calcineurin mutants is tightly associated with abnormal cytosolic calcium accumulation and vacuolar calcium storage capacity deficiency. Our findings provide insights into how the original recognized antifungal drug target-calcineurin regulates intracellular calcium homeostasis for cell survival and may have important implications for antifungal therapy and clinical drug administration. Taylor & Francis 2021-04-12 /pmc/articles/PMC8043181/ /pubmed/33843471 http://dx.doi.org/10.1080/21505594.2021.1909954 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Zhang, Chi Ren, Yiran Gu, Huiyu Gao, Lu Zhang, Yuanwei Lu, Ling Calcineurin-mediated intracellular organelle calcium homeostasis is required for the survival of fungal pathogens upon extracellular calcium stimuli |
title | Calcineurin-mediated intracellular organelle calcium homeostasis is required for the survival of fungal pathogens upon extracellular calcium stimuli |
title_full | Calcineurin-mediated intracellular organelle calcium homeostasis is required for the survival of fungal pathogens upon extracellular calcium stimuli |
title_fullStr | Calcineurin-mediated intracellular organelle calcium homeostasis is required for the survival of fungal pathogens upon extracellular calcium stimuli |
title_full_unstemmed | Calcineurin-mediated intracellular organelle calcium homeostasis is required for the survival of fungal pathogens upon extracellular calcium stimuli |
title_short | Calcineurin-mediated intracellular organelle calcium homeostasis is required for the survival of fungal pathogens upon extracellular calcium stimuli |
title_sort | calcineurin-mediated intracellular organelle calcium homeostasis is required for the survival of fungal pathogens upon extracellular calcium stimuli |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043181/ https://www.ncbi.nlm.nih.gov/pubmed/33843471 http://dx.doi.org/10.1080/21505594.2021.1909954 |
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