ArticleNature communications2018
PHA-4/FoxA senses nucleolar stress to regulate lipid accumulation in Caenorhabditis elegans.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 64 citations in OpenAlex.
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- PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons inGenes & development · 2026Article
- General transcription factor IIIAa regulates the transcription of somatic 5S rRNA and influences embryonic organ development in zebrafish.Marine life science & technology · 2026Article
- Longevity-promoting mitochondrial unfolded protein response activation requires elements of the PeBoW complex.Genes & development · 2026Article
- RPL5 deficiency-induced ribosomal stress targets a select subset of proteins and inhibits the PI3K-Akt-mTOR signaling pathway to eradicate leukemia stem cells.Cell death & disease · 2025Article
- Determination of FAT-1 desaturase activity and substrate preference.Journal of lipid research · 2025Article
- A nitrogen deprivation gradient triggers transcriptional reprogramming for lipid biosynthesis in Auxenochlorella pyrenoidosa.Scientific reports · 2025Article
- PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons ofbioRxiv : the preprint server for biology · 2025Article
- Mechanism of parent-of-origin effects revealed by multi-omic data in euro-chinese hybrid pigs.Nature communications · 2025Article
- Phenotypic tolerance for rDNA copy number variation within the natural range of C. elegans.PLoS genetics · 2025Article
- AI-powered omics-based drug pair discovery for pyroptosis therapy targeting triple-negative breast cancer.Nature communications · 2024Article
- Nucleolar stress induces nucleolar stress body formation via the NOSR-1/NUMR-1 axis in Caenorhabditis elegans.Nature communications · 2024Article
- LET-767 determines lipid droplet protein targeting and lipid homeostasis.The Journal of cell biology · 2024Article
- Identification of genetic suppressors for a BSCL2 lipodystrophy pathogenic variant in Caenorhabditis elegans.Disease models & mechanisms · 2024Article
- Analysis of translesion polymerases in colorectal cancer cells following cetuximab treatment: A network perspective.Cancer medicine · 2024Article
- RNA-seq analysis-based study on the effects of gestational diabetes mellitus on macrosomia.Frontiers in endocrinology · 2024Article
- Opposing action of the FLR-2 glycoprotein hormone and DRL-1/FLR-4 MAP kinases balance p38-mediated growth and lipid homeostasis in C. elegans.PLoS biology · 2023Article
- Muscleblind-1 interacts with tubulin mRNAs to regulate the microtubule cytoskeleton in C. elegans mechanosensory neurons.PLoS genetics · 2023Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
The primary function of the nucleolus is ribosome biogenesis, which is an extremely energetically expensive process. Failures in ribosome biogenesis cause nucleolar stress with an altered energy status. However, little is known about the underlying mechanism linking nucleolar stress to energy metabolism. Here we show that nucleolar stress is triggered by inactivation of RSKS-1 (ribosomal protein S6 kinase), RRP-8 (ribosomal RNA processing 8), and PRO-2/3 (proximal proliferation), all of which are involved in ribosomal RNA processing or inhibition of rDNA transcription by actinomycin D (AD), leading to excessive lipid accumulation in Caenorhabditis elegans. The transcription factor PHA-4/FoxA acts as a sensor of nucleolar stress to bind to and transactivate the expression of the lipogenic genes pod-2 (acetyl-CoA carboxylase), fasn-1 (fatty acid synthase), and dgat-2 (diacylglycerol O-acyltransferase 2), consequently promoting lipid accumulation. Importantly, inactivation of pha-4 or dgat-2 is sufficient to abolish nucleolar stress-induced lipid accumulation and prolonged starvation survival. The results revealed a distinct PHA-4-mediated lipogenesis pathway that senses nucleolar stress and shifts excessive energy for storage as fat.
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Registered trials
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