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Cited by 19Lipid metabolism and biosynthesisSphingolipid Metabolism and SignalingCancer, Lipids, and Metabolism

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DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes

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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·2022·eLife
DOI 10.7554/elife.77665PMC PMC9342972

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Abstract

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.

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Metadata

Authors
Mondal, S., Kinatukara, P., Singh, S., Shambhavi, S., Patil, G. S., Dubey, N., Singh, S. H., Pal, B., Shekar, P. C., Kamat, S. S., & Sankaranarayanan, R.
Affiliations
  • Centre for Cellular and Molecular Biology (IN)
  • Indian Institute of Science Education and Research Pune (IN)
Corresponding author
Sankaranarayanan, Rajan
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2022-06-29
Volume
11
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.77665
PMC
PMC9342972
OpenAlex
W4283706325
Cited by
19
References
2
Citations by year
2026: 4 · 2025: 9 · 2024: 4 · 2023: 2
FWCI
1.59
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Council for Scientific and Industrial Research (CSIR), India
  • Department of Biotechnology, Ministry of Science and Technology, India
  • University Grants Commission
  • DBT/Wellcome Trust India Alliance Fellowship (IA/I/15/2/502058)
  • Department of Science and Technology, Ministry of Science and Technology, India (SR/FST/LSII-043/2016)
  • J.C. Bose Fellowship
  • NCP under health care theme project
  • Centre of Excellence Project
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
diacylglycerol, lipid homeostasis, endoplasmic reticulum stress, triglyceride synthesis, osmoadaptation, yeast, lipidomics
MeSH terms
Animals, Diglycerides, Homeostasis, Saccharomyces cerevisiae, Triglycerides, Lipid Metabolism, Mice

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