Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
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
_version_ 1784760934860849152
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
work_keys_str_mv AT mondalsudipta dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes
AT kinatukarapriyadarshan dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes
AT singhshubham dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes
AT shambhavisakshi dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes
AT patilgajanans dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes
AT dubeynoopur dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes
AT singhsalamherojeet dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes
AT palbiswajit dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes
AT shekarpchandra dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes
AT kamatsiddheshs dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes
AT sankaranarayananrajan dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes