Mito-ParMnem1
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB76267 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Bam files containing mitochondrial alignments, extracted from CPCGene Whole Genome Alignments
| EGAD00001003360 | EGA
Project description:VCF files containing mitochondrial variant calls using MToolbox
| EGAD00001003361 | EGA
Project description:Knowledge about the functions of individual proteins on a systems-wide level is crucial to fully understand molecular mechanisms underlying cellular processes. A considerable part of the proteome across all organisms is still poorly characterized. Mass spectrometry is an efficient technology for the global study of proteins. One of the most prominent methods for accurate proteome-wide quantification is stable isotope labeling by amino acids in cell culture (SILAC). However, application of SILAC to prototrophic organisms such as Saccharomyces cerevisiae, also known as baker's yeast, is compromised since they are able to synthesize all amino acids on their own. Here, we describe an advanced strategy, termed 2nSILAC, that allows for in vivo labeling of prototrophic baker's yeast using heavy arginine and lysine under fermentable and respiratory growth conditions making it a suitable tool for the global study of protein functions. This generic 2nSILAC strategy allows for directly using and systematically screening yeast mutant strain collections available to the scientific community. We exemplarily demonstrate its high potential by analyzing the effects of mitochondrial gene deletions in mitochondrial fractions using quantitative mass spectrometry revealing the role of Coi1 for the assembly of cytochrome c oxidase (respiratory chain complex IV).
2020-01-24 | PXD010019 | Pride
Project description:The long non-coding RNA NEAT1 (nuclear enriched abundant transcript 1) nucleates the formation of paraspeckles, which constitute a type of nuclear body that has multiple roles in gene expression. How the NEAT1 gene itself is regulated and how paraspeckles communicate with other cell compartments remains poorly understood. Here we identify regulators of NEAT1 transcription using an endogenous NEAT1 promoter-driven EGFP reporter in human cells coupled with genome-wide RNAi screens. In addition to transcription factors and chromatin modulators, the screens unexpectedly yielded gene candidates involved in mitochondrial functions as essential regulators of NEAT1 expression and paraspeckle formation. Mitochondrial defects altered NEAT1 transcription via ATF2 and subsequently uncoupled 3’ end processing of NEAT1_1 from its long isoform to favour NEAT1_2 production, which is key for generating elongated paraspeckles that have different features from the regular, globular bodies. Correspondingly, NEAT1 depletion has profound effects on mitochondrial dynamics and function by altering sequestration of mRNAs of mitochondrial genes enriched in paraspeckles. Overall, our data provided a rich resource for understanding NEAT1 and paraspeckle regulation, and revealed an unexpected crosstalk between cytoplasmic organelles and nuclear bodies.
2018-11-06 | GSE110775 | GEO
Project description:Somatic mitochondrial DNA (mtDNA) mutations contribute to the pathogenesis of age-related disorders, including myelodysplastic syndromes (MDS). The accumulation of mitochondria harboring mtDNA mutations in patients with these disorders suggests a failure of normal mitochondrial quality-control systems. The mtDNA-mutator mice acquire somatic mtDNA mutations via a targeted defect in the proofreading function of the mtDNA polymerase, PolgA, and develop macrocyticanemia similar to that of patients with MDS. We observed an unexpected defect in clearance of dysfunctional mitochondria at specific stages during erythroid maturation in hematopoietic cells from aged mtDNA-mutator mice. Mechanistically, aberrant activation of mechanistic target of rapamycin signaling and phosphorylation of uncoordinated 51-like kinase (ULK) 1 in mtDNA-mutator mice resulted in proteasome mediated degradation of ULK1 and inhibition of autophagy in erythroid cells. To directly evaluate the consequence of inhibiting autophagy on mitochondrial function in erythroid cells harboring mtDNA mutations in vivo, we deleted Atg7 from erythroid progenitors of wildtype and mtDNA-mutator mice. Genetic disruption of autophagy did not cause anemia in wild-type mice but accelerated the decline in mitochondrial respiration and development of macrocytic anemia in mtDNA-mutator mice. These findings highlight a pathological feedback loop that explains how dysfunctional mitochondria can escape autophagy-mediated degradation and propagate in cells predisposed to somatic mtDNA mutations, leading to disease. We used microarrays to identify expression profiles and pathways that are differentially activated or suppressed in Ter119+ bone marrow cells isolated from phlebotomized wildtype or Polg mutant mice
2015-04-21 | E-GEOD-57761 | biostudies-arrayexpress
Project description:Balancing of mitochondrial translation through METTL8-mediated m3C modification of mitochondrial tRNAs
| PRJEB45091 | ENA
Project description:To identify mutations that occurred in the nuclear and mitochondrial DNA of the yeast subjected to mtDNA base editing or Mito-BE screen, we performed whole-genome sequencing of cultured yeast cells after isolation of mitochondrial DNA.
2024-11-01 | E-MTAB-13701 | biostudies-arrayexpress
Project description:Genetic variation in mitochondrial DNA (mtDNA) provides adaptive potential although the underlying genetic architecture of fitness components within mtDNAs is not known. To dissect functional variation within mtDNAs, we first identified naturally occurring mtDNAs that conferred high or low fitness in Saccharomyces cerevisiae by comparing growth in strains containing identical nuclear genotypes but different mtDNAs. During respiratory growth under temperature and oxidative stress conditions, mitotype effects were largely independent of nuclear genotypes even in the presence of mito-nuclear interactions. Recombinant mtDNAs were generated to determine fitness components within high- and low-fitness mtDNAs. Based on phenotypic distributions of isogenic strains containing recombinant mtDNAs, we found that multiple loci contributed to mitotype fitness differences. These mitochondrial loci interacted in epistatic, nonadditive ways in certain environmental conditions. Mito-mito epistasis (i.e., nonadditive interactions between mitochondrial loci) influenced fitness in progeny from four different crosses, suggesting that mito-mito epistasis is a widespread phenomenon in yeast and other systems with recombining mtDNAs. Furthermore, we found that interruption of coadapted mito-mito interactions produced recombinant mtDNAs with lower fitness. Our results demonstrate that mito-mito epistasis results in functional variation through mitochondrial recombination in fungi, providing modes for adaptive evolution and the generation of mito-mito incompatibilities.
| S-EPMC5937185 | biostudies-other
Project description:Extrinsic skin ageing converges on the dermis, a post-mitotic tissue compartment consisting of extracellular matrix and long-lived fibroblasts prone to damage accumulation and maladaptation. Aged human fibroblasts exhibit mitochondrial and nuclear dysfunctions, but it is unclear whether these are cause or consequence of ageing. We report on a systematic study of human dermal fibroblasts retrieved from female donors aged 20-67 years and analyzed in primary culture at low population doubling precluding replicative senescence. Genome-wide array analysis failed to detect significant (>2-fold) age-related expression changes for individual genes, but gene set enrichment analysis revealed down regulation of many genes involved in mitochondrial metabolism and respiratory electron transport, extracellular matrix maintenance, cell cycle progression and protein translation. Consistent with these changes, mitochondrial content, respiratory function and cell proliferation declined with donor age. This was associated with inadequate nuclear mito-biogenesis, hypo- phosphorylation of AMP-dependent protein kinase alpha and upregulation of the alpha2-isoform, suggesting that inadequate mito-nuclear signalling could be the leading event entailing decreased expression of mitochondrial genes and compensatory down regulation of proliferation and protein synthesis. The comparatively few genes exhibiting age-associated up regulation were associate with cholesterol metabolism, immune reactions and mRNA processing, possibly also reflecting adaptation to inadequate mitochondrial function. Donors: 15 human female donors included in the study were aged 20, 21, 23, 26, 26, 40, 41, 42, 43, 49, 60, 62, 63, 64 and 67 years, thus covering the age spectrum 20 – 67 years and providing five biological replicates for each of the age groups “young” (20-30 years), “middle” (40-50 years) and “old” (60-70 years). Human dermal fibroblasts were isolated from skin specimen removed in the course of cosmetic surgery from the bottom side of female breast. Isolation and primary culture of the cells followed published procedures (Tigges and others 2013). Cells were not expanded beyond 12 population doublings, while replicative cell cycle arrest was determined to not occur before 40 population doublings.
2014-04-08 | E-GEOD-55118 | biostudies-arrayexpress
Project description:Slowing down mRNA translation in either the cytoplasm or the mitochondria are both conserved longevity mechanisms. Here, we found a non-interventional natural correlation of mitochondrial and cytoplasmic ribosomal proteins when looking at mouse population genetics, suggesting a mito-cytoplasmic translational balance. Additionally, inhibiting mitochondrial translation in C. elegans in turn reduced cytoplasmic translation and repressed growth pathways while upregulating stress responses at both proteome and transcriptome levels. This coordinated repression of cytoplasmic translation is dependent on the atf-5/Atf4 transcription factor and is conserved in mammalian cells upon inhibiting mitochondrial translation pharmacologically with the antibiotic doxycycline. Lastly, extending this to a mammalian setting using doxycycline-treated germ-free mice, we found repressed cytoplasmic translation and ribosomal proteins in liver. These data demonstrate that inhibiting mitochondrial translation initiates a signaling cascade leading to coordinated repression of cytoplasmic translation, unlike previously described unidirectional cyto-to-mito translational communication in yeast, which can be targeted to promote healthy aging.
2019-12-11 | GSE122097 | GEO