Search results for "mitochondrial"
showing 10 items of 919 documents
Mcl-1 and Bok transmembrane domains : Unexpected players in the modulation of apoptosis
2020
The Bcl-2 protein family comprises both proand antiapoptotic members that control the permeabilization of the mitochondrial outer membrane, a crucial step in the modulation of apoptosis. Recent research has demonstrated that the carboxyl-terminal transmembrane domain (TMD) of some Bcl-2 protein family mem-bers can modulate apoptosis; however, the transmembrane interactome of the antiapoptotic protein Mcl-1 remains largely unexplored. Here, we demonstrate that the Mcl-1 TMD forms homooligomers in the mitochondrial membrane, competes with full-length Mcl-1 protein with regards to its antiapoptotic function, and induces cell death in a Bok-dependent manner. While the Bok TMD oligomers locate p…
Phosphoproteomics of the developing heart identifies PERM1 - An outer mitochondrial membrane protein.
2021
Heart development relies on PTMs that control cardiomyocyte proliferation, differentiation and cardiac morphogenesis. We generated a map of phosphorylation sites during the early stages of cardiac postnatal development in mice; we quantified over 10,000 phosphorylation sites and 5000 proteins that were assigned to different pathways. Analysis of mitochondrial proteins led to the identification of PGC-1- and ERR-induced regulator in muscle 1 (PERM1), which is specifically expressed in skeletal muscle and heart tissue and associates with the outer mitochondrial membrane. We demonstrate PERM1 is subject to rapid changes mediated by the UPS through phosphorylation of its PEST motif by casein ki…
Cytotoxic activity of the histone deacetylase 3-Selective inhibitor Pojamide on MDA-MB-231 triple-negative breast cancer cells
2019
We examined the effects of the ferrocene-based histone deacetylase-3 inhibitor Pojamide (N1-(2-aminophenyl)-N8-ferrocenyloctanediamide) and its two derivatives N1-(2-aminophenyl)-N6-ferrocenyladipamide and N1-(2-aminophenyl)-N8-ferroceniumoctanediamide tetrafluoroborate on triple-negative MDA-MB-231 breast cancer cells. Viability/growth assays indicated that only the first two compounds at 70 &mu
Possible A2E Mutagenic Effects on RPE Mitochondrial DNA from Innovative RNA-Seq Bioinformatics Pipeline
2020
Mitochondria are subject to continuous oxidative stress stimuli that, over time, can impair their genome and lead to several pathologies, like retinal degenerations. Our main purpose was the identification of mtDNA variants that might be induced by intense oxidative stress determined by N-retinylidene-N-retinylethanolamine (A2E), together with molecular pathways involving the genes carrying them, possibly linked to retinal degeneration. We performed a variant analysis comparison between transcriptome profiles of human retinal pigment epithelial (RPE) cells exposed to A2E and untreated ones, hypothesizing that it might act as a mutagenic compound towards mtDNA. To optimize analysis, we propo…
The Absence of HIF-1α Increases Susceptibility to Leishmania donovani Infection via Activation of BNIP3/mTOR/SREBP-1c Axis
2020
Summary: Hypoxia-inducible factor-1 alpha (HIF-1α) is considered a global regulator of cellular metabolism and innate immune cell functions. Intracellular pathogens such as Leishmania have been reported to manipulate host cell metabolism. Herein, we demonstrate that myeloid cells from myeloid-restricted HIF-1α-deficient mice and individuals with loss-of-function HIF1A gene polymorphisms are more susceptible to L. donovani infection through increased lipogenesis. Absence of HIF-1α leads to a defect in BNIP3 expression, resulting in the activation of mTOR and nuclear translocation of SREBP-1c. We observed the induction of lipogenic gene transcripts, such as FASN, and lipid accumulation in inf…
The cellular growth rate controls overall mRNA turnover, and modulates either transcription or degradation rates of particular gene regulons
2015
We analyzed 80 different genomic experiments, and found a positive correlation between both RNA polymerase II transcription and mRNA degradation with growth rates in yeast. Thus, in spite of the marked variation in mRNA turnover, the total mRNA concentration remained approximately constant. Some genes, however, regulated their mRNA concentration by uncoupling mRNA stability from the transcription rate. Ribosome-related genes modulated their transcription rates to increase mRNA levels under fast growth. In contrast, mitochondria-related and stress-induced genes lowered mRNA levels by reducing mRNA stability or the transcription rate, respectively. We also detected these regulations within th…
Vascular ageing and endothelial cell senescence: Molecular mechanisms of physiology and diseases
2016
Ageing leads to a progressive deterioration of structure and function of all organs over the time. During this process endothelial cells undergo senescence and manifest significant changes in their properties, resulting in impairment of the vascular functionality and neo-angiogenic capability. This ageing-dependent impairment of endothelial functions is considered a key factor contributing to vascular dysfunctions, which is responsible of several age-related diseases of the vascular system and other organs. Several mechanisms have been described to control ageing-related endothelial cell senescence including microRNAs, mitochondrial dysfunction and micro environmental stressors, such as hyp…
Combined phylogenetic and morphometric information to delimit and unify the Triatoma brasiliensis species complex and the Brasiliensis subcomplex
2017
Made available in DSpace on 2018-12-11T16:46:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-06-01 “Triatoma brasiliensis species complex” was defined as a monophyletic group of the species: T. brasiliensis, T. juazeirensis, T. melanica, and T. sherlocki. An alternative grouping scheme proposed the concept of “Brasiliensis subcomplex” which included the former species together with T. melanocephala, T. petrocchiae, T. lenti, T. tibiamaculata, and T. vitticeps. To evaluate the relationship among these taxa we combined the results obtained with four mitochondrial genes (12S, 16S, COI and Cytb, adding to 1811 bp) and geometric morphometric analysis of wings and heads. Panstrongylus m…
Small RNA-seq analysis of circulating miRNAs to identify phenotypic variability in Friedreich's ataxia patients.
2018
AbstractFriedreich’s ataxia (FRDA; OMIM 229300), an autosomal recessive neurodegenerative mitochondrial disease, is the most prevalent hereditary ataxia. In addition, FRDA patients have shown additional non-neurological features such as scoliosis, diabetes, and cardiac complications. Hypertrophic cardiomyopathy, which is found in two thirds of patients at the time of diagnosis, is the primary cause of death in these patients. Here, we used small RNA-seq of microRNAs (miRNAs) purified from plasma samples of FRDA patients and controls. Furthermore, we present the rationale, experimental methodology, and analytical procedures for dataset analysis. This dataset will facilitate the identificatio…
Ancient pigs reveal a near-complete genomic turnover following their introduction to Europe
2019
International audience; Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local Euro-pean wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hyp…