CHIP/CHN-1 and UFD-2 C. Elegans Proteomes
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Caenorhabditis Elegans
SUBMITTER: 
Hendrik Nolte
LAB HEAD: Marcus Krüger
PROVIDER: PXD028023 | Pride | 2022-05-04
REPOSITORIES: Pride
Similar Datasets
Project description:The metabolic plasticity of mitochondria supports cell development and differentiation and ensures cell survival under stress. The peptidase OMA1 regulates mitochondrial morphology and stress signaling and orchestrates tumorigenesis and cell fate decisions in a cell and tissue-specific manner. Here, we have used unbiased systemic approaches to demonstrate that OMA1-dependent cell fate decisions are under metabolic control. A metabolism-focus CRISPR screen combined with an integrated analysis of human expression data unraveled a protective role of OMA1 against DNA damage. Nucleotide deficiencies induced by chemotherapeutic agents promote the selective, p53-dependent apoptosis of cells lacking OMA1. The protective effect of OMA1 does not depend on OMA1 activation nor on OMA1-mediated OPA1 and DELE1 processing. OMA1-deficient cells have reduced glycolytic capacity and accumulate OXPHOS proteins upon DNA damage. OXPHOS inhibition restores glycolysis and confers resistance against DNA damage. Thus, metabolic cues determine cell fate decisions by OMA1, which sheds new light on the role of OMA1 in cancerogenesis.
2023-04-04 | PXD036595 | Pride
Project description:MDVs are implicated in diverse physiological processes e.g. mitochondrial quality control and are linked to various neurodegenerative diseases. However, their specific cargo composition and complex molecular biogenesis is still unknown. Here we report for the first time the proteome and lipidome of steady-state TOMM20+-MDVs. We identified 106 novel high confidence MDV cargoes and verified several candidates by super-resolution microscopy including 5 members of the TOM import complex. Additionally, we demonstrate that MDVs deliver fully assembled protein complexes like the TOM complex for lysosomal degradation, thus filling a crucial mitochondrial quality control niche. Moreover, we show key biogenesis steps of MDVs starting with the MIRO1/2-dependent formation of thin membrane protrusions pulled along microtubule filaments, followed by MID49/MID51/MFF-dependent recruitment of the dynamin family GTPase DRP1 and finally DRP1-dependent scission. We conclude that catalysing scission during MDV biogenesis demonstrates a novel function of DRP1, distinct from its role in mitochondrial division.
2021-09-28 | PXD023077 | Pride
Project description:Cardiomyopathy and heart failure are common manifestations in mitochondrial disease caused by deficiencies in the oxidative phosphorylation system of mitochondria (OXPHOS). Here, we demonstrate that the cardiac-specific loss of the assembly factor Cox10 of the cytochrome c oxidase causes mitochondrial cardiomyopathy in mice, which is associated with OXPHOS deficiency, lysosomal defects and an aberrant mitochondrial morphology and ultrastructure. We demonstrate activation of the mitochondrial peptidase Oma1 in Cox10-/- mice, which results in mitochondrial fragmentation and induction of the integrated stress response (ISR) along the Oma1-Dele1-Atf4 signalling axis. Ablation of Oma1 or Dele1 in Cox10-/- mice aggravates cardiomyopathy. ISR inhibition impairs the cardiac glutathione metabolism, decreases the levels of the glutathione peroxidase Gpx4 and increases lipid peroxidation in the heart, ultimately culminating in ferroptosis. Our results demonstrate a protective role of the Oma1-mediated ISR in mitochondrial cardiomyopathy and link ferroptosis to OXPHOS deficiency and mitochondrial disease.
2022-07-27 | PXD031641 | Pride
Project description:Folding of newly synthesized proteins poses challenges for a functional proteome. Dedicated protein quality control (PQC) systems promote either the folding of nascent polypeptides at ribosomes or, if this fails, ensure their degradation. While well studied for cytosolic protein biogenesis, it is not understood how these processes work for mitochondrially-encoded proteins, key subunits of the oxidative phosphorylation system (OXPHOS). Here, we identify dedicated hubs in proximity to mitoribosomal tunnel exits coordinating mitochondrial translation, protein import, assembly, and protein turnover. Conserved prohibitin/m-AAA protease supercomplexes and the availability of assembly chaperones determine the fate of newly synthesized proteins by molecular triaging. The localization of these competing activities in vicinity to the mitoribosomal tunnel exit allows for a prompt decision whether newly synthesized proteins are fed into OXPHOS assembly or degraded. This repository hosts the whole proteome of PHB1/2 deletion cells and is related to other repositories:
2023-08-14 | PXD043668 | Pride
Project description:Hyaluronan receptor LYVE-1 is expressed by liver sinusoidal endothelial cells (LSEC), lymphatic endothelial cells and specialized macrophages. Besides binding hyaluronan, LYVE-1 mediates adhesion of leukocytes and cancer cells to endothelial cells. Here, we analyzed the impact of LYVE-1 on physiological liver functions and metastasis. Mice with deficiency of Lyve-1 (Lyve-1 KO) were analyzed using histology, immunofluorescence, RNA sequencing, plasma proteomics and flow cytometry. Liver metastasis was studied by intrasplenic/intravenous injection of melanoma (B16F10luc2, WT31) or colorectal carcinoma (MC38) cell lines. Results: Hepatic architecture, liver size, endothelial differentiation and angiocrine functions were unaltered in Lyve-1 KO mice. Hyaluronan plasma levels were significantly increased in Lyve-1-KO mice; besides, plasma proteomics revealed increased carbonic anhydrase-2 and decreased FXIIIA, potential modulators of metastatis. Furthermore, gene expression analysis of LSEC indicated regulation of immunological pathways. Therefore, liver metastasis of a highly and of a weekly immunogenic tumor, i.e. melanoma and colorectal carcinoma (CRC), was analyzed in Lyve-1 KO mice. Hepatic metastasis of B16F10 luc2 and WT31 melanoma cells, but not MC38 CRC cells, was significantly reduced in Lyve-1 KO mice. While short-term adhesion assays with B16F10 luc2 cells in vivo did not show differences between Lyve-1 KO and wild-type mice, increased numbers of resident hepatic CD4+, CD8+ and regulatory T cells were detected in Lyve-1 KO livers. In addition, iron deposition was detected in F4/80+ liver macrophages known to exert pro-inflammatory effects. Conclusions: LYVE-1 deficiency controlled hepatic metastasis in a tumor cell-specific manner reducing hepatic metastasis of melanoma, but not CRC. Anti-tumorigenic effects are likely due to enhancement of the resident hepatic immune microenvironment.
2023-03-11 | PXD032717 | Pride
Project description:Folding of newly synthesized proteins poses challenges for a functional proteome. Dedicated protein quality control (PQC) systems promote either the folding of nascent polypeptides at ribosomes or, if this fails, ensure their degradation. While well studied for cytosolic protein biogenesis, it is not understood how these processes work for mitochondrially-encoded proteins, key subunits of the oxidative phosphorylation system (OXPHOS). Here, we identify dedicated hubs in proximity to mitoribosomal tunnel exits coordinating mitochondrial translation, protein import, assembly, and protein turnover. Conserved prohibitin/m-AAA protease supercomplexes and the availability of assembly chaperones determine the fate of newly synthesized proteins by molecular triaging. The localization of these competing activities in vicinity to the mitoribosomal tunnel exit allows for a prompt decision whether newly synthesized proteins are fed into OXPHOS assembly or degraded. This repository contains the results of the FLAG-based enrichment of the native prohibitin complex. Please note that we measured elution either with LDS sample buffer or using FLAG-peptides. In the published study, the LDS elution buffer was shown.
2023-08-14 | PXD043671 | Pride
Project description:Coenzyme Q (or ubiquinone) is a redox-active lipid, which serves as universal electron carrier in the mitochondrial respiratory chain and antioxidant in the plasma membrane limiting lipid peroxidation and ferroptosis. Mechanisms allowing cellular coenzyme Q distribution after synthesis within mitochondria are not understood. Here, we identify the cytosolic lipid transfer protein STARD7 as a critical and limiting factor of intracellular coenzyme Q transport. Dual localization of STARD7 to the intermembrane space of mitochondria and the cytosol upon cleavage by the rhomboid protease PARL ensures the synthesis of coenzyme Q in mitochondria and its transport to the plasma membrane. While cytosolic STARD7 overexpression protects against ferroptosis, it limits CoQ abundance in mitochondria and respiratory cell growth, illustrating the need to coordinate CoQ synthesis and cellular distribution by PARL-mediated STARD7 processing. Our findings highlight the antioxidant function of mitochondrial CoQ against ferroptosis and identify PARL and STARD7 as promising targets to interfere with ferroptosis. The repository contains raw files and methods for project 0112 (brain – whole proteomics) and 0176 (spatial proteomics). The labeling of the raw files and the experiment – raw file matches are available in the individual search zip files. The individual sections are accompanied with the project identifier.
2022-11-12 | PXD033064 | Pride
Project description:Replication and expression of the mitochondrial genome depend on the sufficient supply ofnucleotide building blocks to mitochondria. Dysregulated nucleotide metabolism is detrimental tomitochondrial genomes and can destabilise mitochondrial DNA and trigger inflammation. Here, wereport that a mitochondrial nucleoside diphosphate kinase, NME6, supplies mitochondria withpyrimidine ribonucleotides to drive the transcription of mitochondrial genes. Perturbation of NME6leads to the depletion of mitochondrial transcripts, destabilisation of the electron transport chainand impaired oxidative phosphorylation. These deficiencies are rescued upon supplementation withpyrimidine ribonucleosides. Moreover, NME6 is required for the maintenance of mitochondrial DNAwhen the access to cytosolic pyrimidine deoxyribonucleotides is limited. Our results, therefore, shedlight on the importance of mitochondrial ribonucleotide salvage for the synthesis of RNA andmitochondrial gene expression.The repository contains two internal projects which are identified by the internal IDs: 0187 and 0196. The raw files are indicated by the internal ID, and each Supplementary Table contains a reference to the internal ID. The project with the ID 0187 contains whole cell (WC) and immunoprecipitation (IP) data. Please see the file: SampleNamesForProjects.xlsx for more details.
2023-05-04 | PXD038391 | Pride
Project description:Proteomic analysis of bioreactor supernatants can inform on cellular metabolic status, viability, and productivity, as well as product quality, which can in turn help optimize bioreactor operation. Incubating mammalian cells in bioreactors requires the addition of polymeric surfactants such as Pluronic F68, which reduce the sheer stress caused by agitation. However, these surfactants are incompatible with mass spectrometry proteomics and must be eliminated during sample preparation. Here, we compared four different sample preparation methods to eliminate Pluronic F68 from filtered bioreactor supernatant samples: organic solvent precipitation; filter-assisted sample preparation (FASP); S-Trap; and single-pot, solid-phase, sample preparation (SP3). We found that SP3 and S-Trap substantially reduced or eliminated the polymer(s), but S-Trap provided the most robust clean-up and highest quality data. Additionally, we observed that SP3 sample preparation of our samples and in other published datasets was associated with partial alkylation of cysteines, which could impact the confidence and robustness of protein identification and quantification. Finally, we observed that several commercial mammalian cell culture media and media supplements also contained polymers with a similar mass spectrometry profile to Pluronic F68, and we suggest that proteomic analyses in these media will also benefit from the use of S-Trap sample preparation.
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