Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD004666
PROVIDER: PRJNA335626 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3956440.fastq.gz | Fastqsanger.gz | |||
| SRR3956450.fastq.gz | Fastqsanger.gz | |||
| SRR3956460.fastq.gz | Fastqsanger.gz | |||
| SRR3956441.fastq.gz | Fastqsanger.gz | |||
| SRR3956451.fastq.gz | Fastqsanger.gz |
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Project description:Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the mitochondrial respiratory chain (RC) and is composed of 44 different subunits in humans, making it one of the largest known multi-subunit membrane protein complexes. Complex I exists in supercomplex forms with RC complexes III and IV, which are together required for the generation of a transmembrane proton gradient used for the synthesis of ATP. Complex I is also a major source of damaging reactive oxygen species in the cell and its dysfunction is associated with mitochondrial disease, Parkinson’s disease and aging. Bacterial and human complex I share 14 core subunits that are essential for enzymatic function, however the role and requirement of the remaining 30 human accessory subunits is unclear. The incorporation of accessory subunits into the complex increases the energetic cost to the cell and has necessitated the involvement of a suite of assembly factors for complex I biogenesis. We used gene-editing to generate human knockout cell lines for each accessory subunit. We found that 25 subunits are strictly required for assembly of a functional complex and one subunit is essential for cell viability. Quantitative proteomic analysis of all 30 cell lines revealed that subunits belong to discrete complex I modules, and their loss affects the stability of subunits within these modules. Known assembly factors were found to correlate with most modules. Analysis of proteomic changes when other modules were destabilised revealed ATP5SL and DMAC1 as novel factors required to assemble the distal portion of the complex I membrane arm. Our results demonstrate the broad importance of accessory subunits in the structure and function of human complex I. Coupling gene-editing technology with large-scale proteomics represents a powerful tool for dissecting large multi-subunit complexes and enabling the study of complex dysfunction at a cellular level.
2016-09-26 | PXD004666 | Pride
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
2020-12-03 | GSE162543 | GEO
Project description:Protein homeostasis in eukaryotic organelles and their progenitor prokaryotes is regulated by a series of ATP-dependent proteases including the caseinolytic protease complex (ClpXP). In chloroplasts, ClpXP has essential roles in organelle biogenesis and maintenance , but the significance of the plant mitochondrial ClpXP remains unknown and factors that aid coordination of nuclear and mitochondrial encoded subunits for complex assembly in mitochondria await discovery. In this study, we generated knock-out lines of the single copy mitochondrial Clp protease subunit, CLPP2, in Arabidopsis thaliana. They have higher abundance of transcripts from mitochondrial genes encoding OXPHOS protein complexes, while transcripts for nuclear genes encoding other subunits of the same complexes showed no change in transcript abundance. In contrast, the protein abundance of specific nuclear-encoded subunits in OXPHOS complexes I and V increased in knockouts, without accumulation of mitochondrial-encoded counterparts in the same complex. Protein complexes mainly or wholly encoded in the nucleus were unaffected. Analysis of protein import, assembly and function of Complex I revealed that while function was retained, protein homeostasis was disrupted through slower assembly, leading to accumulation of soluble subcomplexes of nuclear-encoded subunits after import. It is proposed that CLPP contributes to the mitochondrial protein degradation network through supporting coordination and assembly of protein complexes encoded across mitochondrial and nuclear genomes.
2019-12-13 | GSE141942 | GEO
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
2020-11-25 | GSE162118 | GEO
Project description:Background: Transcription control of mitochondrial metabolism is essential for cellular function. A better understanding of this process will aid the elucidation of mitochondrial disorders, in particular of the many genetically unsolved cases of oxidative phosphorylation (OXPHOS) deficiency. Yet, to date only few studies have investigated nuclear gene regulation in the context of OXPHOS deficiency. In this study, we combined RNA sequencing of human complex I-deficient patient cells across 32 conditions of perturbed mitochondrial metabolism, with a comprehensive analysis of gene expression patterns, co-expression calculations and transcription factor binding sites. Results: Our analysis shows that OXPHOS genes have a significantly higher co-expression with each other than with other genes, including mitochondrial genes. We found no evidence for complex-specific mRNA expression regulation in the tested cell types and conditions: subunits of different OXPHOS complexes are similarly (co-)expressed and regulated by a common set of transcription factors. However, we did observe significant differences between the expression of OXPHOS complex subunits compared to assembly factors, suggesting divergent transcription programs. Furthermore, complex I co-expression calculations identified 684 genes with a likely role in OXPHOS biogenesis and function. Analysis of evolutionarily conserved transcription factor binding sites in the promoters of these genes revealed almost all known OXPHOS regulators (including GABP, NRF1/2, SP1, YY1, E-box factors) and a set of six yet uncharacterized candidate transcription factors (ELK1, KLF7, SP4, EHF, ZNF143, and EL2). Conclusions: OXPHOS genes share an expression program distinct from other mitochondrial genes, indicative of targeted regulation of this mitochondrial sub-process. Within the subset of OXPHOS genes we established a difference in expression between subunits and assembly factors. Most transcription regulators of genes that co-express with complex I are well-established factors for OXPHOS biogenesis. For the remaining six factors we here suggest for the first time a link with transcription regulation in OXPHOS deficiency. RNA-SEQ of whole cell RNA in 2 control and 2 complex I deficient patient fibroblast cell lines treated with 4 compounds in duplicate, resulting in a total of 2x2x4x2=32 samples
2015-08-31 | E-GEOD-65634 | biostudies-arrayexpress
Project description:Mitochondria are complex organelles containing 13 proteins encoded by mitochondrial DNA and over 1000 proteins encoded on nuclear DNA. Many mitochondrial proteins are associated with the inner or outer mitochondrial membranes, either peripherally or as integral membrane proteins, while others reside in either of the two soluble mitochondrial compartments, the mitochondrial matrix and the intermembrane space. The biogenesis of the five complexes of the oxidative phosphorylation system are exemplars of this complexity. These large multi-subunit complexes are built through the tightly controlled coalescence of more than 80 proteins with both membrane integral and peripheral associations, with progression between different assembly steps dependent on soluble, membrane integral and peripherally associated assembly factor proteins. Understanding the membrane association of subunits and assembly factors during each assembly step is critical to understanding OXPHOS complex biogenesis. Here we couple sodium carbonate extraction with quantitative mass spectrometry to track changes in the membrane association of the mitochondrial proteome across multiple human complex III knockout cell lines. In addition to identifying the membrane association status of over 840 human mitochondrial proteins, we identify a previously undetected intermediate step of complex III biogenesis. Sodium carbonate extraction with quantitative mass spectrometry (SCE-MS) is thus an easy to apply tool with general utility in the study of mitochondrial respiratory chain biogenesis.
2022-03-23 | PXD028935 | Pride
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
2022-02-18 | GSE196754 | GEO
Project description:Chromatin remodeling complexes control the availability of DNA binding sites to transcriptional regulators. Two distinct forms of the major SWI/SNF-related complex that have different activities in vitro can be distinguished by the presence of specific accessory subunits. In Drosophila, the core Brahma complex associates either with Osa to form the BAP complex, or with Bap170 and Bap180 to form the PBAP complex. Mutations affecting the core subunits have stronger developmental phenotypes than osa mutations; these differences could be due to PBAP complex activity . We have generated mutations in the genes encoding the PBAP-specific subunits Bap170 and Bap180 in order to study their functions in vivo. Bap180 is not essential for viability, but is required in ovarian follicle cells for normal eggshell development. Bap170 is necessary to stabilize the Bap180 protein; however, a mutant form that retains this function is sufficient for survival and fertility. The two subunits act redundantly to allow metamorphosis; using gene expression profiling of double mutants, we have found that the PBAP complex regulates genes involved in tissue remodeling and immune system function. Finally, we have generated mutants that lack Bap170, Bap180 and Osa in the germline to demonstrate that the function of the core Brahma complex in oogenesis does not require any of these accessory subunits. To study PBAP specific subunits Bap170 and Bap180 role in Drosophila melanogaster development Experiment Overall Design: Two males and two females for each genotype (wild type and bap170;bap180 double mutant) were processed at white prepupae stage (0 hour APF)
2009-10-21 | E-GEOD-11825 | biostudies-arrayexpress
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO