Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1002987 | ENA |
REPOSITORIES: ENA
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Project description:Accumulating evidence suggests that mitochondrial dysfunction underlies the pathophysiology of bipolar disorder (BD) and schizophrenia (SZ). We performed large-scale DNA microarray analysis of postmortem brains of patients with BD or SZ, and examined expression patterns of mitochondria-related genes. We found a global down-regulation of mitochondrial genes, such as those encoding respiratory chain components, in BD and SZ samples, even after the effect of sample pH was controlled. However, this was likely due to the effects of medication. Medication-free patients with BD showed tendency of up-regulation of subset of mitochondrial genes. Our findings support the mitochondrial dysfunction hypothesis of BD and SZ pathologies. However, it may be the expression changes of a small fraction of mitochondrial genes rather than the global down-regulation of mitochondrial genes. Our findings warrant further study of the molecular mechanisms underlying mitochondrial dysfunction in BD and SZ. Keywords: disease state analysis A total of 102 postmortem brains obtained from the Stanley Medical Research Institute were used for DNA microarray analysis. Fresh frozen samples were used for RNA extraction.
2008-09-03 | E-GEOD-12649 | biostudies-arrayexpress
Project description:Hexadecenal, a trans (-2,3-) unsaturated fatty aldehyde, is an intermediate of the sphingolipid degradation pathway. This pathway, induced during cellular stress, involves the conversion of sphingosine-1-phosphate to hexadecenal by Sphingosine-1-Phosphate-Lyase (SPL) in humans and DPL1 in yeast. Hexadecenal is further metabolized to hexadecenoic acid by Fatty Aldehyde Dehydrogenase (ALDH3A2 in humans and HFD1 in yeast). Trans-2-hexadecenal (t-2-hex), has been found to induce mitochondrial dysfunction in a conserved manner from yeast to humans. However, the specific mechanisms and biological targets underlying this lipid-induced mitochondrial inhibition remain largely unknown. In this study, we employed unbiased transcriptomic approaches using the Saccharomyces cerevisiae yeast model to elucidate the principal mechanisms and biological targets associated with t-2-hex-induced mitochondrial dysfunction. To investigate the effects of t-2-hex, we utilized an hfd1 mutant strain lacking the HFD1 gene. This strain exhibited increased sensitivity to t-2-hex treatment compared to wild-type cells. Exponentially growing hfd1 mutant cells were exposed to 100 μM t-2-hex for a duration of 3 hours, while control cells were incubated with the solvent dimethyl sulfoxide (DMSO), in which hexadecenal is dissolved. Total RNA was extracted from both treated and control cells for high-throughput sequencing analysis. Through transcriptomic profiling, we aimed to identify differentially expressed genes, pathways, and regulatory networks associated with t-2-hex-induced mitochondrial dysfunction in yeast. This study provides a comprehensive analysis of the transcriptional response to t-2-hex treatment, shedding light on the molecular mechanisms and potential biological targets underlying lipid-induced mitochondrial dysfunction.
2023-07-31 | E-MTAB-13188 | biostudies-arrayexpress
Project description:Mitochondrial DNA (mtDNA) quantitative and qualitative defects have been associated with impaired human embryonic development, but the underlying mechanisms remain unknown. By using human embryos affected by mitochondrial disorders as models of mitochondrial dysfunction, we compared gene expression between 9 mitochondrial embryos (carriers of a pathogenic variant in a mtDNA or a nuclear gene coding for a mitochondrial protein) to 33 controls. Transcriptomic analyses performed by RNA-Sequencing revealed a similar global transcriptional repression in mitochondrial embryos affecting a significant proportion of differentiation factors and nuclear genes encoding mitochondrial proteins. If oxidative phosphorylation was at the top of the most significant deregulated pathways, cell survival and autophagy were found to be significantly decreased in these embryos, questioning their viability. Differentially expressed genes identified in this study represent good predictive biomarkers of mitochondrial dysfunction and should be tested as markers of preimplantation development.
2023-02-27 | E-MTAB-11531 | biostudies-arrayexpress
Project description:Accumulating evidence suggests that mitochondrial dysfunction underlies the pathophysiology of bipolar disorder (BD) and schizophrenia (SZ). We performed large-scale DNA microarray analysis of postmortem brains of patients with BD or SZ, and examined expression patterns of mitochondria-related genes. We found a global down-regulation of mitochondrial genes, such as those encoding respiratory chain components, in BD and SZ samples, even after the effect of sample pH was controlled. However, this was likely due to the effects of medication. Medication-free patients with BD showed tendency of up-regulation of subset of mitochondrial genes. Our findings support the mitochondrial dysfunction hypothesis of BD and SZ pathologies. However, it may be the expression changes of a small fraction of mitochondrial genes rather than the global down-regulation of mitochondrial genes. Our findings warrant further study of the molecular mechanisms underlying mitochondrial dysfunction in BD and SZ. Keywords: disease state analysis
2008-09-03 | GSE12649 | GEO
Project description:Mitochondrial DNA (mtDNA) encodes essential components of the respiratory chain and loss of mtDNA leads to mitochondrial dysfunction and neurodegeneration. Mitochondrial transcription factor A (TFAM) is an essential component of mtDNA replication and a regulator of mitochondrial copy number in cells. Studies have shown that TFAM knockdown leads to mitochondrial dysfunction and respiratory chain deficiencies. Using gene expression analysis, we aimed to investigate the effects of mtDNA dysfunction in the CNS at the molecular level. We used microarray analysis to investigate gene expression in cases of mitochondrial dysfunction in the CNS. RNA was purified from the late third instar larval CNS from control larvae, or larvae over-expressing mitochondrial transcription factor A (TFAM) in post-mitotic neurons using the neuron specific driver nsyb-Gal4. Three replicates are included for each condition.
2013-12-20 | E-GEOD-53509 | biostudies-arrayexpress
Project description:As the central hub metabolic organ bodily, the liver is paramount to keep whole-body energy homeostasis. Further, mitochondria are the central metabolic hub within cells to connect the main catabolized, energy production, and hormonal signaling pathways. It is evident that mitochondrial dysfunction may play a critical role in the development of NASH. Accordingly, understanding the underlying mechanisms of mitochondrial dysfunction is of importance to develop therapies for NASH. Here, we report that mice with hepatocyte-specific deletion of Tid1, encoding a mitochondrial cochaperone, tended to develop NASH-dependent HCC. The hepatocellular nodules were developed in 3-month DEN-treated Tid1-/- mice. At the age of 6 months, the DEN-treated Tid1-/- mice showed a higher number of tumors and greater tumor size than the DEN-treated Tid1+/- mice, followed by the DEN-treated WT mice. To gain insights into the mRNA changes during NASH-HCC progress, we performed an RNA-seq analysis with livers collected from 6-month DEN-treated mice.
2022-07-02 | E-MTAB-9974 | biostudies-arrayexpress
Project description:Behavioural fever and its underlying molecular mechanisms
| PRJNA146979 | ENA
Project description:Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells (Affymetrix)
| PRJNA268305 | ENA
Project description:Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells (miRNA)
| PRJNA268313 | ENA