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PHA-4/FoxA senses nucleolar stress to regulate lipid accumulation in Caenorhabditis elegans
- Source :
- Nature Communications, Vol 9, Iss 1, Pp 1-17 (2018), Nature Communications
- Publication Year :
- 2018
- Publisher :
- Nature Publishing Group, 2018.
-
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.<br />Nucleolar stress can disrupt ribosome biogenesis and in turn energy metabolism and lipid storage, but how this is regulated is unclear. Here, the authors show in C. elegans that the transcription factor PHA-4/FOXA acts as a sensor for nucleolar stress and can regulate expression of lipogenic genes
- Subjects :
- 0301 basic medicine
Nucleolus
Science
General Physics and Astronomy
Ribosome biogenesis
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
0302 clinical medicine
Transcription (biology)
lcsh:Science
Transcription factor
Caenorhabditis elegans
Diacylglycerol kinase
Multidisciplinary
biology
Chemistry
fungi
food and beverages
General Chemistry
Ribosomal RNA
biology.organism_classification
Cell biology
030104 developmental biology
Ribosomal protein s6
lcsh:Q
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....a06a88b207624aebb0fdd01273a84f94