Caenorhabditis elegans
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ABSTRACT:
PROVIDER: PRJNA389732 | ENA |
REPOSITORIES: ENA
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Project description:The endoplasmic reticulum (ER) is an organelle associated with lipid metabolism. However, the involvement of the ER in nutritional status-dependent energy homeostasis is largely unknown. The results of this study demonstrate that IRE-1, an ER protein known to be involved in the unfolded protein response, and HSP-4, an ER chaperone, regulate expression of the novel fasting-induced lipases FIL-1 and FIL-2, which induce fat granule hydrolysis upon fasting in C. elegans. RNAi and ectopic expression experiments demostrated that FIL-1 and FIL-2 are both necessary and sufficient for fasting-induced fat granule breakdown. Failure of ire-1 and hsp-4 mutant animals to hydrolyze fat granules during starvation impaired their motility, which was rescued by glucose supplementation of their media, implicating the importance of ire-1/hsp-4-dependent lipolysis for energy supply from stored fat during fasting. Taken together, these data suggest that the ER-resident proteins IRE-1 and HSP-4 are key nutritional sensors that modulate expression of inducible lipases to maintain whole-body energy homeostasis in C. elegans. Synchronized L4 worms were divided into well-fed and 6 hours fasted samples for RNA extraction and hybridization on an Agilent microarray.
2010-05-08 | E-GEOD-15656 | biostudies-arrayexpress
Project description:The endoplasmic reticulum (ER) is an organelle associated with lipid metabolism. However, the involvement of the ER in nutritional status-dependent energy homeostasis is largely unknown. The results of this study demonstrate that IRE-1, an ER protein known to be involved in the unfolded protein response, and HSP-4, an ER chaperone, regulate expression of the novel fasting-induced lipases FIL-1 and FIL-2, which induce fat granule hydrolysis upon fasting in C. elegans. RNAi and ectopic expression experiments demostrated that FIL-1 and FIL-2 are both necessary and sufficient for fasting-induced fat granule breakdown. Failure of ire-1 and hsp-4 mutant animals to hydrolyze fat granules during starvation impaired their motility, which was rescued by glucose supplementation of their media, implicating the importance of ire-1/hsp-4-dependent lipolysis for energy supply from stored fat during fasting. Taken together, these data suggest that the ER-resident proteins IRE-1 and HSP-4 are key nutritional sensors that modulate expression of inducible lipases to maintain whole-body energy homeostasis in C. elegans.
2009-04-15 | GSE15656 | GEO
Project description:Cold affects many aspects of biology, medicine, agriculture and industry. Here, we identify a conserved endoplasmic reticulum (ER) stress response, distinct from the canonical unfolded protein response, which maintains lipid homeostasis during extreme cold stress. We establish that the ER stress sensor IRE-1 is critical for resistance to extreme cold and is activated by cold temperature. Specifically, neuronal IRE-1 signals via JNK-1 and neuropeptide-mediated signalling to regulate lipid composition throughout the animal. The requirement of this cold-response pathway can be bypassed by supplementation with unsaturated fatty acids or by altering the diet . Altogether, our findings define an ER-centric conserved organism-wide cold stress response pathway, consisting of sensors, effectors and signalling moieties, which control adaptation to cold throughout the organism. Better understanding of the molecular basis of cold adaptation is crucial for the design of safe and optimal use of cold conditions on live organisms and samples, and for the development of better treatments for hypothermia. Conclusions: Our study represents a detailed analysis of C.elegans transcriptomes during cold stress, with biological replicates, generated by RNA-seq technology.
2022-11-15 | GSE193923 | GEO
Project description:All animals must maintain genome and proteome integrity, especially when experiencing endogenous or exogenous stress. To cope, organisms have evolved sophisticated and conserved response systems: unfolded protein responses (UPRs) ensure proteostasis while the DNA damage response (DDR) maintains genome integrity. Emerging evidence suggests that UPRs and DDRs crosstalk, but the extent of crosstalk remains poorly understood. Here, we demonstrate that inactivation of the DNA primases pri-1 and pri-2, which synthesize RNA primers at replication forks and whose inactivation causes DNA damage, activates the UPR of the endoplasmic reticulum (UPR-ER) in Caenorhabditis elegans, with especially strong activation in the germline. We observed activation of both the inositol-requiring-enzyme 1 (ire-1) and the protein kinase RNA-like ER kinase (PEK-1) branches of the UPR-ER. Interestingly, activation of the UPR-ER output gene hsp-4/BiP was partially independent of its canonical activators, ire-1 and xbp-1, and instead required the third branch of the UPR-ER, atf-6, suggesting functional redundancy. We further found that primase depletion specifically induces the UPR-ER, but not the mechanistically distinct cytosolic or mitochondrial UPRs, suggesting that primase inactivation causes compartment-specific rather than global stress. Functionally, loss of ire-1 or pek-1 sensitized animals to replication stress caused by hydroxyurea. Finally, transcriptome analysis of pri-1 embryos revealed several deregulated processes that could cause UPR-ER activation, including protein glycosylation, calcium signaling, and fatty acid desaturation. Together, our data show that the UPR-ER, but not other UPRs, responds to replication fork stress and that the UPR-ER is required to alleviate this stress.
2024-01-17 | GSE225569 | GEO
Project description:Lipid biosynthesis coordinates a Mitochondrial to Cytosolic Stress Response
| PRJNA326871 | ENA
Project description:Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes SKN-1, IRE-1, and XBP-1
| PRJNA342039 | ENA
Project description:Metabolic diseases are strongly associated with endoplasmic reticulum (ER) stress. Upon ER stress, the unfolded protein response (UPR) is activated to limit cellular damage. However, escalating cellular UPR response weakens with age. Here, we show that 5-day-old Caenorhabditis elegans fed a bacteria diet with 2% glucose (high glucose diet, HGD-5) extend their lifespan while shortening the lifespan of 1-day-old (HGD-1) animals. We observed a metabolic shift in HGD-1 as glucose and fertility synergistically prolonged the lifespan of HGD-5, independently of DAF-16. Notably, we identified that UPR stress sensors ATF-6 and PEK-1 extended the longevity of HGD-5 worms, while the ire-1 ablation drastically increased HGD-1 lifespan. Based on these observations, we postulate that HGD activates the otherwise quiescent UPR in aged worms to overcome ageing-related stress and restore ER homeostasis. In contrast, young animals subjected to HGD provokes unresolved ER stress, conversely leading to a detrimental stress response.
2021-08-31 | GSE182981 | GEO
Project description:S4, a sulfonamide drug, has been confirmed to induce apoptosis and autophagy in cancer cells. Immunogenic cell death is a special cell death type which is closely related to apoptosis and autophagy. We performed RNA-seq to determine the impact of S4 on global gene expression profile in LN229 cells. Our results show that S4 induces immunogenic cell death via the response to endoplasmic reticulum stress.
2022-06-13 | GSE205538 | GEO
Project description:Tocotrienol Rich Fraction (TRF) Modulates Genes Expression in Oxidative Stress-Induced Caenorhabditis elegans
| PRJNA393168 | ENA
Project description:We recently used a genome-wide screen to demonstrate that numr-1/2 is activated by disruption of RNA metabolism. To investigate numr-1/2 regulation and identify modulators of nucleic acid metabolism, we screened over 40,000 compounds and extracts from commercial and natural product libraries for numr-1/2p::GFP activation. Fungal toxin chaetocin was the most potent and least toxic numr-1/2 inducer. RT-qPCR demonstrates that chaetocin induces numr-1/2 and another stress-responsive SR-like protein gene (W03G1.5) in C. elegans over 50-fold within 45 minutes without affecting expression of canonical heat shock, osmotic stress, endoplasmic reticulum stress, mitochondrial stress, or detoxification response genes. Chaetocin does not activate other metal-responsive genes and actually reduces expression of metallothionein gene mtl-2 and fluorescence of mtl-2p::GFP consistent with repression of mtl-2 transcription. Along with a similar HMTase inhibitor from the same fungal origin - Chetomin, and two synthetic S-methyl-products of Chaetocin and Chetomin, respectively, we tested the expression profile at 5h and 12h post treatment at 500 nM concentration in HCT116 colorectal carcinoma cell line. Both S-methyl-products showed no significant activity or any detectable statistically significant changes in expression compared to the vehicle control. The parent compounds induced a number of expression changes consistent with effects on the stress-response genes in HCT116 cells.
2024-05-15 | GSE232639 | GEO