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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2022-06-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/77665 |
| _version_ | 1811236260174364672 |
|---|---|
| author | Sudipta Mondal Priyadarshan Kinatukara Shubham Singh Sakshi Shambhavi Gajanan S Patil Noopur Dubey Salam Herojeet Singh Biswajit Pal P Chandra Shekar Siddhesh S Kamat Rajan Sankaranarayanan |
| author_facet | Sudipta Mondal Priyadarshan Kinatukara Shubham Singh Sakshi Shambhavi Gajanan S Patil Noopur Dubey Salam Herojeet Singh Biswajit Pal P Chandra Shekar Siddhesh S Kamat Rajan Sankaranarayanan |
| author_sort | Sudipta Mondal |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T12:06:09Z |
| format | Article |
| id | doaj.art-b886c84527514994b0ad7e38a33b0dba |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:06:09Z |
| publishDate | 2022-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b886c84527514994b0ad7e38a33b0dba2022-12-22T03:33:42ZengeLife Sciences Publications LtdeLife2050-084X2022-06-011110.7554/eLife.77665DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotesSudipta Mondal0https://orcid.org/0000-0002-3923-7449Priyadarshan Kinatukara1https://orcid.org/0000-0003-2210-2369Shubham Singh2Sakshi Shambhavi3https://orcid.org/0000-0002-8852-1542Gajanan S Patil4Noopur Dubey5Salam Herojeet Singh6Biswajit Pal7P Chandra Shekar8Siddhesh S Kamat9https://orcid.org/0000-0001-6132-7574Rajan Sankaranarayanan10https://orcid.org/0000-0003-4524-9953CSIR-Centre for Cellular and Molecular Biology, Hyderabad, IndiaCSIR-Centre for Cellular and Molecular Biology, Hyderabad, IndiaDepartment of Biology, Indian Institute of Science Education and Research (IISER), Pune, IndiaCSIR-Centre for Cellular and Molecular Biology, Hyderabad, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, IndiaCSIR-Centre for Cellular and Molecular Biology, Hyderabad, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, IndiaCSIR-Centre for Cellular and Molecular Biology, Hyderabad, IndiaCSIR-Centre for Cellular and Molecular Biology, Hyderabad, IndiaCSIR-Centre for Cellular and Molecular Biology, Hyderabad, IndiaCSIR-Centre for Cellular and Molecular Biology, Hyderabad, IndiaDepartment of Biology, Indian Institute of Science Education and Research (IISER), Pune, IndiaCSIR-Centre for Cellular and Molecular Biology, Hyderabad, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, IndiaChain-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.https://elifesciences.org/articles/77665DIP2diacylglycerolfatty acyl-AMP ligasemembrane contact siteOpisthokontatriacylglycerol |
| spellingShingle | Sudipta Mondal Priyadarshan Kinatukara Shubham Singh Sakshi Shambhavi Gajanan S Patil Noopur Dubey Salam Herojeet Singh Biswajit Pal P Chandra Shekar Siddhesh S Kamat Rajan Sankaranarayanan DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes eLife DIP2 diacylglycerol fatty acyl-AMP ligase membrane contact site Opisthokonta triacylglycerol |
| 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 | DIP2 diacylglycerol fatty acyl-AMP ligase membrane contact site Opisthokonta triacylglycerol |
| url | https://elifesciences.org/articles/77665 |
| work_keys_str_mv | AT sudiptamondal dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes AT priyadarshankinatukara dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes AT shubhamsingh dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes AT sakshishambhavi dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes AT gajananspatil dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes AT noopurdubey dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes AT salamherojeetsingh dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes AT biswajitpal dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes AT pchandrashekar dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes AT siddheshskamat dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes AT rajansankaranarayanan dip2isauniqueregulatorofdiacylglycerollipidhomeostasisineukaryotes |