Pexophagy-driven redox imbalance promotes virus-induced ferroptosis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1255113 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33299668_1.fastq.gz | Fastqsanger.gz | |||
| SRR33299668_2.fastq.gz | Fastqsanger.gz | |||
| SRR33299669_1.fastq.gz | Fastqsanger.gz | |||
| SRR33299669_2.fastq.gz | Fastqsanger.gz | |||
| SRR33299670_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 48 |
Similar Datasets
Project description:Peroxisomes are critical organelles that maintain cellular redox homeostasis. Many viruses induce oxidative stress and degrade peroxisomes, but the mechanisms and consequences remain unclear. In this study, we systematically investigate how virus-induced pexophagy regulates peroxisome homeostasis. Using Newcastle disease virus (NDV) as a model, we demonstrate that NDV infection triggers excessive ROS production, activating the phosphorylation and peroxisomal localization of Ataxia-telangiectasia mutated (ATM). Activated ATM promotes the interaction between the peroxisomal receptor PEX5 and the autophagy receptor p62, driving pexophagy. Pexophagy-mediated peroxisome degradation leads to excess active iron and ROS accumulation, contributing to NDV-induced ferroptosis. Notably, this mechanism is shared by other viruses, such as vesicular stomatitis virus (VSV) and H9N2 avian influenza virus (IAV). Our study provides new insights into how virus-induced pexophagy disrupts redox homeostasis to promote ferroptosis, highlighting a novel link between viral infection, peroxisome degradation, and programmed cell death.
2025-04-29 | GSE295522 | GEO
Project description:Redox Imbalance in COVID-19 Pathophysiology
| PRJNA873078 | ENA
Project description:Ferroptosis is a type of programmed cell death caused by disruption of redox homeostasis, and is closely linked to amino acid metabolism. Yin Yang 2 (YY2) and its homolog Yin Yang 1 (YY1) are members of the YY family with high homology, especially in their zinc-finger domains. Furthermore, they share consensus DNA binding motif. In contrast with the oncogenic YY1, increasing evidences have demonstrated the tumor suppressive effect of YY2; however, at present, little is known about its biological and pathological functions. Here we found that YY2 induces tumor cells ferroptosis and subsequently, suppresses tumorigenesis, by inhibiting SLC7A11 transcription, leading to the decreased glutathione biosynthesis. Furthermore, we reveal that YY2 and YY1 bind competitively to SLC7A11 promoter and antagonistically regulate tumor cells ferroptosis, thus suggesting the molecular mechanism underlying their opposite regulation on tumorigenesis. Moreover, we showed that mutations of YY2 zinc-finger domains in clinical cancer patients abrogated YY2/SLC7A11 axis and tumor cells ferroptosis. Together, these results provide a new insight regarding the regulatory mechanism of ferroptosis, and a mechanistic explanation regarding the tumor suppressive effect of YY2. Furthermore, our findings demonstrate that homeostasis between YY1 and YY2 is crucial for maintaining redox homeostasis in tumor cells.
2022-05-11 | GSE184138 | GEO
Project description:Neurons are unique among all human cell types in their high energy demand, long lifespans and rich lipid contents. As such, neurons exhibit unique vulnerability to oxidative stress caused by redox imbalance in aging and neurodegenerative diseases (NDDs). To systematically identify regulators of neuronal survival under oxidative stress and regulators of neuronal redox homeostasis, we conducted multiple survival- and FACS-based genome-wide screens in human iPSC-derived neurons, using our functional genomics toolkit including a previously established CRISPRi approach and a newly developed CRISPRa approach. So far, these are the first genome-wide screens in human neurons. Our results revealed that inhibiting glycosphingolipids (GSLs) degradation by depletion of prosaposin (PSAP) drives the formation of lipofuscins in neurons which leads to iron accumulation and strongly induces ROS production that oxidizing lipids and leads to neuronal ferroptosis under oxidative stress. We also conducted single cell CROP-seq screens that revealed transcriptomic signatures of NDD-associated genes. These datasets are freely available through our open-access database CRISPRbrain.
2020-06-23 | GSE152988 | GEO
Project description:The pathophysiologic significance of redox imbalance is unquestionable as numerous reports and topic reviews indicate alterations in redox parameters during corona virus disease 2019 (COVID-19). However, a more comprehensive understanding of redox-related parameters in the context of COVID-19-mediated inflammation and pathophysiology is required. COVID-19 subjects (n=64) and control subjects (n=19) were enrolled, and blood was drawn within 72 hours of diagnosis. Serum multiplex assay and buffy coat cell mRNA sequencing was performed. Oxidant/free radical (electron paramagnetic resonance (EPR) spectroscopy, nitrite-nitrate assay) and antioxidant (ferrous reducing ability of serum assay and high-performance liquid chromatography) were performed. Multivariate analyses were performed to evaluate potential of indicated parameters to predict clinical outcome. Significantly greater levels of multiple inflammatory and vascular markers were quantified in the subjects admitted to the ICU compared to non-ICU subjects. Gene set enrichment analyses indicated significant enhancement of oxidant related pathways and biochemical assays confirmed a significant increase in free radical production and uric acid reduction in COVID-19 subjects. Multivariate analyses confirmed a positive association between serum levels of VCAM-1, ICAM-1 and a negative association between the abundance of one electron oxidants (detected by ascorbate radical formation) and mortality in COVID subjects while IL-17c and TSLP levels predicted need for intensive care in COVID-19 subjects.
2022-09-21 | GSE211979 | GEO
Project description:Homeostasis imbalance of YY2 and YY1 promotes tumor growth by manipulating ferroptosis
| PRJNA763289 | ENA
Project description:AS-exos exacerbates microglial ferroptosis-driven neuroinflammation
| PRJNA1046021 | ENA
Project description:Clostridium thermocellum is a promising CBP candidate organism capable of directly converting lignocellulosic biomass to ethanol. Low yields, productivities and growth inhibition prevent industrial deployment of this organism for commodity fuel production. Symptoms of potential redox imbalance such as incomplete substrate utilization, and fermentation products characteristic of overflow metabolism, have been observed during growth. This perceived redox imbalance may be in part responsible for the mentioned bioproductivity limitations. Toward better understanding the redox metabolism of C. thermocellum, we analyzed gene expression, using microarrays, during addition of two stress chemicals (methyl viologen and hydrogen peroxide) which we observed to change fermentation redox potential.
2015-07-29 | GSE71465 | GEO
Project description:Ferroptosis is a non-apoptotic form of regulated cell death triggered by the discoordination of regulatory redox mechanisms culminating in massive peroxidation of polyunsaturated phospholipids. The development of the concept of ferroptosis stemmed from an active search for alternatives to apoptosis in cancer cells. Ferroptosis inducers have shown remarkable effectiveness in killing tumor cells in vitro, yet with no obvious success in experimental animal models, with a notable exception of immune-deficient mice 1,2. This suggests the potential poorly understood contribution of ferroptosis on immune cells. Pathologically activated neutrophils (PMN), termed myeloid-derived suppressor cells (PMN-MDSC), are major negative regulators of anti-tumor immunity3-5. Here, we found that PMN-MDSC in the tumor microenvironment (TME), spontaneously die by ferroptosis. While decreasing the presence of PMN-MDSC, ferroptosis induces the release of oxygenated lipids and limits mouse and human T cell activity. In immune-competent mice, genetic and pharmacological inhibition of ferroptosis abrogates suppressive activity of PMN-MDSC, reduces tumor progression, and synergizes with immune checkpoint blockade (ICB) to suppress the tumor growth. In contrast, induction of ferroptosis in immune-competent mice promotes tumor growth. Thus, ferroptosis is a unique and targetable immunosuppressive mechanism of PMN-MDSC in the TME that can be pharmacologically modulated to limit tumor progression.
2022-09-24 | GSE213861 | GEO
Project description:Ferroptosis is a non-apoptotic form of regulated cell death triggered by the discoordination of regulatory redox mechanisms culminating in massive peroxidation of polyunsaturated phospholipids. The development of the concept of ferroptosis stemmed from an active search for alternatives to apoptosis in cancer cells. Ferroptosis inducers have shown remarkable effectiveness in killing tumor cells in vitro, yet with no obvious success in experimental animal models, with a notable exception of immune-deficient mice 1,2. This suggests the potential poorly understood contribution of ferroptosis on immune cells. Pathologically activated neutrophils (PMN), termed myeloid-derived suppressor cells (PMN-MDSC), are major negative regulators of anti-tumor immunity3-5. Here, we found that PMN-MDSC in the tumor microenvironment (TME), spontaneously die by ferroptosis. While decreasing the presence of PMN-MDSC, ferroptosis induces the release of oxygenated lipids and limits mouse and human T cell activity. In immune-competent mice, genetic and pharmacological inhibition of ferroptosis abrogates suppressive activity of PMN-MDSC, reduces tumor progression, and synergizes with immune checkpoint blockade (ICB) to suppress the tumor growth. In contrast, induction of ferroptosis in immune-competent mice promotes tumor growth. Thus, ferroptosis is a unique and targetable immunosuppressive mechanism of PMN-MDSC in the TME that can be pharmacologically modulated to limit tumor progression.
2022-09-19 | GSE205371 | GEO