DIP2 is a unique regulator of diacylglycerol lipid homeostasis in eukaryotes.

Autor:	Mondal S; CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India., Kinatukara P; CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India., Singh S; Department of Biology, Indian Institute of Science Education and Research (IISER), Pune, India., Shambhavi S; CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India., Patil GS; CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India., Dubey N; CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India., Singh SH; CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India., Pal B; CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India., Shekar PC; CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India., Kamat SS; Department of Biology, Indian Institute of Science Education and Research (IISER), Pune, India., Sankaranarayanan R; CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2022 Jun 29; Vol. 11. Date of Electronic Publication: 2022 Jun 29.
DOI:	10.7554/eLife.77665
Abstrakt:	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. Competing Interests: SM, PK, SS, SS, GP, ND, SS, BP, PS, SK No competing interests declared, RS Reviewing editor, eLife (© 2022, Mondal, Kinatukara et al.)
Databáze:	MEDLINE
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