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DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes
Chain-length-specific subsets of diacylglycerol (DAG) lipids are proposed to regulate differential physiological responses ranging from signal transduction to modulation of the membrane properties. However, the mechanism or molecular players regulating the subsets of DAG species remain unknown. Here...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342972/ https://www.ncbi.nlm.nih.gov/pubmed/35766356 http://dx.doi.org/10.7554/eLife.77665 |
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author | Mondal, Sudipta Kinatukara, Priyadarshan Singh, Shubham Shambhavi, Sakshi Patil, Gajanan S Dubey, Noopur Singh, Salam Herojeet Pal, Biswajit Shekar, P Chandra Kamat, Siddhesh S Sankaranarayanan, Rajan |
author_facet | Mondal, Sudipta Kinatukara, Priyadarshan Singh, Shubham Shambhavi, Sakshi Patil, Gajanan S Dubey, Noopur Singh, Salam Herojeet Pal, Biswajit Shekar, P Chandra Kamat, Siddhesh S Sankaranarayanan, Rajan |
author_sort | Mondal, Sudipta |
collection | PubMed |
description | Chain-length-specific subsets of diacylglycerol (DAG) lipids are proposed to regulate differential physiological responses ranging from signal transduction to modulation of the membrane properties. However, the mechanism or molecular players regulating the subsets of DAG species remain unknown. Here, we uncover the role of a conserved eukaryotic protein family, DISCO-interacting protein 2 (DIP2) as a homeostatic regulator of a chemically distinct subset of DAGs using yeast, fly, and mouse models. Genetic and chemical screens along with lipidomics analysis in yeast reveal that DIP2 prevents the toxic accumulation of specific DAGs in the logarithmic growth phase, which otherwise leads to endoplasmic reticulum stress. We also show that the fatty acyl-AMP ligase-like domains of DIP2 are essential for the redirection of the flux of DAG subspecies to storage lipid, triacylglycerols. DIP2 is associated with vacuoles through mitochondria–vacuole contact sites and such modulation of selective DAG abundance by DIP2 is found to be crucial for optimal vacuole membrane fusion and consequently osmoadaptation in yeast. Thus, the study illuminates an unprecedented DAG metabolism route and provides new insights on how cell fine-tunes DAG subspecies for cellular homeostasis and environmental adaptation. |
format | Online Article Text |
id | pubmed-9342972 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-93429722022-08-02 DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes Mondal, Sudipta Kinatukara, Priyadarshan Singh, Shubham Shambhavi, Sakshi Patil, Gajanan S Dubey, Noopur Singh, Salam Herojeet Pal, Biswajit Shekar, P Chandra Kamat, Siddhesh S Sankaranarayanan, Rajan eLife Biochemistry and Chemical Biology Chain-length-specific subsets of diacylglycerol (DAG) lipids are proposed to regulate differential physiological responses ranging from signal transduction to modulation of the membrane properties. However, the mechanism or molecular players regulating the subsets of DAG species remain unknown. Here, we uncover the role of a conserved eukaryotic protein family, DISCO-interacting protein 2 (DIP2) as a homeostatic regulator of a chemically distinct subset of DAGs using yeast, fly, and mouse models. Genetic and chemical screens along with lipidomics analysis in yeast reveal that DIP2 prevents the toxic accumulation of specific DAGs in the logarithmic growth phase, which otherwise leads to endoplasmic reticulum stress. We also show that the fatty acyl-AMP ligase-like domains of DIP2 are essential for the redirection of the flux of DAG subspecies to storage lipid, triacylglycerols. DIP2 is associated with vacuoles through mitochondria–vacuole contact sites and such modulation of selective DAG abundance by DIP2 is found to be crucial for optimal vacuole membrane fusion and consequently osmoadaptation in yeast. Thus, the study illuminates an unprecedented DAG metabolism route and provides new insights on how cell fine-tunes DAG subspecies for cellular homeostasis and environmental adaptation. eLife Sciences Publications, Ltd 2022-06-29 /pmc/articles/PMC9342972/ /pubmed/35766356 http://dx.doi.org/10.7554/eLife.77665 Text en © 2022, Mondal, Kinatukara et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Mondal, Sudipta Kinatukara, Priyadarshan Singh, Shubham Shambhavi, Sakshi Patil, Gajanan S Dubey, Noopur Singh, Salam Herojeet Pal, Biswajit Shekar, P Chandra Kamat, Siddhesh S Sankaranarayanan, Rajan DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes |
title | DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes |
title_full | DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes |
title_fullStr | DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes |
title_full_unstemmed | DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes |
title_short | DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes |
title_sort | dip2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342972/ https://www.ncbi.nlm.nih.gov/pubmed/35766356 http://dx.doi.org/10.7554/eLife.77665 |
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