ArticleCell death and differentiation2018
Diacylglycerol triggers Rim101 pathway-dependent necrosis in yeast: a model for lipotoxicity.
Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
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- Exploring the interplay between yeast cell membrane lipid adaptation and physiological response to acetic acid stress.Applied and environmental microbiology · 2024Article
- Spatially Resolved Molecular Analysis of Host Response to Medical Device Implantation Using the 3D OrbiSIMS Highlights a Critical Role for Lipids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Diacylglycerol metabolism and homeostasis in fungal physiology.FEMS yeast research · 2024Review
- Quantifying yeast lipidomics by high-performance thin-layer chromatography (HPTLC) and comparison to mass spectrometry-based shotgun lipidomics.Microbial cell (Graz, Austria) · 2024Article
- A dynamic actin cytoskeleton is required to prevent constitutive VDAC-dependent MAPK signalling and aberrant lipid homeostasis.iScience · 2023Article
- MoLrp1-mediated signaling induces nuclear accumulation of MoMsn2 to facilitate fatty acid oxidation for infectious growth of the rice blast fungus.Plant communications · 2023Article
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- Functional genomics and metabolomics advance the ethnobotany of the Samoan traditional medicine "matalafi".Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Reprogrammed lipid metabolism protects inner nuclear membrane against unsaturated fat.Developmental cell · 2021Article
- Excess diacylglycerol at the endoplasmic reticulum disrupts endomembrane homeostasis and autophagy.BMC biology · 2020Article
- Tricalbins Contribute to Cellular Lipid Flux and Form Curved ER-PM Contacts that Are Bridged by Rod-Shaped Structures.Developmental cell · 2019Article
- Mechanisms by which PE21, an extract from the white willowOncotarget · 2019Article
- Single-molecule localization microscopy and tracking with red-shifted states of conventional BODIPY conjugates in living cells.Nature communications · 2019Article
- Lipotoxicty in yeast: a focus on plasma membrane signalling and membrane contact sites.FEMS yeast research · 2018Review
- Guidelines and recommendations on yeast cell death nomenclature.Microbial cell (Graz, Austria) · 2018Review
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 6 countries.
Funding
Abstract
The loss of lipid homeostasis can lead to lipid overload and is associated with a variety of disease states. However, little is known as to how the disruption of lipid regulation or lipid overload affects cell survival. In this study we investigated how excess diacylglycerol (DG), a cardinal metabolite suspected to mediate lipotoxicity, compromises the survival of yeast cells. We reveal that increased DG achieved by either genetic manipulation or pharmacological administration of 1,2-dioctanoyl-sn-glycerol (DOG) triggers necrotic cell death. The toxic effects of DG are linked to glucose metabolism and require a functional Rim101 signaling cascade involving the Rim21-dependent sensing complex and the activation of a calpain-like protease. The Rim101 cascade is an established pathway that triggers a transcriptional response to alkaline or lipid stress. We propose that the Rim101 pathway senses DG-induced lipid perturbation and conducts a signaling response that either facilitates cellular adaptation or triggers lipotoxic cell death. Using established models of lipotoxicity, i.e., high-fat diet in Drosophila and palmitic acid administration in cultured human endothelial cells, we present evidence that the core mechanism underlying this calpain-dependent lipotoxic cell death pathway is phylogenetically conserved.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.