ArticleThe Journal of biological chemistry2014
A functional, genome-wide evaluation of liposensitive yeast identifies the "ARE2 required for viability" (ARV1) gene product as a major component of eukaryotic fatty acid resistance.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Insights intomSphere · 2026Article
- Identification of fatty acid metabolism signature genes in patients with pulmonary arterial hypertension using WGCNA and machine learning.The Journal of international medical research · 2024Article
- Lipid scrambling is a general feature of protein insertases.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Lipid scrambling is a general feature of protein insertases.bioRxiv : the preprint server for biology · 2023Article
- Regulated targeting of the monotopic hairpin membrane protein Erg1 requires the GET pathway.The Journal of cell biology · 2022Article
- Loss of SNORA73 reprograms cellular metabolism and protects against steatohepatitis.Nature communications · 2021Article
- Identification of novel genes involved in neutral lipid storage by quantitative trait loci analysis of Saccharomyces cerevisiae.BMC genomics · 2021Article
- An Erg11 lanosterol 14-α-demethylase-Arv1 complex is required for Candida albicans virulence.PloS one · 2020Article
- Database for High Throughput Screening Hits (dHITS): a simple tool to retrieve gene specific phenotypes from systematic screens done in yeast.Yeast (Chichester, England) · 2018Article
- Mice lackingThe Journal of biological chemistry · 2018Article
- Lipid droplet-mediated lipid and protein homeostasis in budding yeast.FEBS letters · 2018Review
- Article
- Yeast Cells Exposed to Exogenous Palmitoleic Acid Either Adapt to Stress and Survive or Commit to Regulated Liponecrosis and Die.Oxidative medicine and cellular longevity · 2018Review
- Recent Advances in Ergosterol Biosynthesis and Regulation Mechanisms inIndian journal of microbiology · 2017Review
- Exacerbating and reversing lysosomal storage diseases: from yeast to humans.Microbial cell (Graz, Austria) · 2017Review
- Proper Sterol Distribution Is Required forG3 (Bethesda, Md.) · 2016Article
- Knockdown of triglyceride synthesis does not enhance palmitate lipotoxicity or prevent oleate-mediated rescue in rat hepatocytes.Biochimica et biophysica acta · 2016Article
- Neuronal deficiency of ARV1 causes an autosomal recessive epileptic encephalopathy.Human molecular genetics · 2016Article
- What's old is new again: yeast mutant screens in the era of pooled segregant analysis by genome sequencing.Microbial cell (Graz, Austria) · 2016Article
- Article
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
The toxic subcellular accumulation of lipids predisposes several human metabolic syndromes, including obesity, type 2 diabetes, and some forms of neurodegeneration. To identify pathways that prevent lipid-induced cell death, we performed a genome-wide fatty acid sensitivity screen in Saccharomyces cerevisiae. We identified 167 yeast mutants as sensitive to 0.5 mm palmitoleate, 45% of which define pathways that were conserved in humans. 63 lesions also impacted the status of the lipid droplet; however, this was not correlated to the degree of fatty acid sensitivity. The most liposensitive yeast strain arose due to deletion of the "ARE2 required for viability" (ARV1) gene, encoding an evolutionarily conserved, potential lipid transporter that localizes to the endoplasmic reticulum membrane. Down-regulation of mammalian ARV1 in MIN6 pancreatic β-cells or HEK293 cells resulted in decreased neutral lipid synthesis, increased fatty acid sensitivity, and lipoapoptosis. Conversely, elevated expression of human ARV1 in HEK293 cells or mouse liver significantly increased triglyceride mass and lipid droplet number. The ARV1-induced hepatic triglyceride accumulation was accompanied by up-regulation of DGAT1, a triglyceride synthesis gene, and the fatty acid transporter, CD36. Furthermore, ARV1 was identified as a transcriptional of the protein peroxisome proliferator-activated receptor α (PPARα), a key regulator of lipid homeostasis whose transcriptional targets include DGAT1 and CD36. These results implicate ARV1 as a protective factor in lipotoxic diseases due to modulation of fatty acid metabolism. In conclusion, a lipotoxicity-based genetic screen in a model microorganism has identified 75 human genes that may play key roles in neutral lipid metabolism and disease.
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Registered trials
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